A Trial to Assess the Efficacy and Safety of 400mg/Day Lacosamide in Subjects With Painful Diabetic Neuropathy

A Multi-center, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of 400mg/Day Lacosamide in Subjects With Painful Distal Diabetic Neuropathy Using Two Different Titration Schemes

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00350103

Enrollment

551

Registered

2006-07-10

Start date

2006-06-30

Completion date

2007-06-29

Last updated

2024-03-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Painful Diabetic Neuropathy

Keywords

Painful Diabetic Neuropathy, Lacosamide

Brief summary

The purpose of this trial is to assess whether 400mg/day of lacosamide is effective in reducing pain caused by distal diabetic neuropathy. Two dose-escalation schemes for lacosamide will be used to further determine the efficacy of the standard scheme and to evaluate the efficacy and safety of a more rapid titration scheme. Subjects will be randomly assigned to one of three treatment groups. Subjects in two of the groups will receive lacosamide at a dose of 400mg/day, but different dose-escalation schemes will be used to reach this final dose. The third group of subjects will receive a placebo. Subjects will have a 2 in 3 (66 %) chance of getting lacosamide. The maximum lacosamide dose in this trial will be 400mg/day. The maximum treatment duration will be 18 weeks, including a two-week Pre-Treatment Phase and a 12 weeks period on a stable dose of lacosamide or placebo.

Interventions

DRUGSPM 929

* Pharmaceutical form: Immediate release film-coated tablets * Concentration: 50mg/ 100mg * Route of administration: Oral use

DRUGPlacebo

* Pharmaceutical form: Immediate release film-coated tablets * Route of administration: Oral use

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subject has had symptoms of painful diabetic neuropathy for at least 6 months and has a diagnosis of diabetes mellitus (Type I or Type II).

Exclusion criteria

* Subject has previously participated in this trial or subject has previously been assigned to treatment in a trial of the drug under investigation in this trial

Design outcomes

Primary

Measure	Time frame	Description
Change in Average Daily Pain Score From Baseline Week to the Last 4 Weeks of the Maintenance Phase	Last 4 weeks of Maintenance Phase, compared to the Baseline Week	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.

Secondary

Measure	Time frame	Description
Time to Sustainable Pain Relief	From start of trial medication intake (Week 0) up to the last 4 weeks of the Maintenance Phase	Time to sustainable pain relief was defined as the time from Baseline to the first day on which there was a ≥1-point improvement over Baseline in the Likert pain score for those subjects for whom there was also ≥30% reduction in average daily pain score over the last 28 days of the Maintenance Phase as compared to Baseline.
Percentage of Subjects With >= 30% or >= 2-point Reduction of with-in Subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of the Maintenance Phase	Baseline week, last 4 weeks of the Maintenance Phase	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening.
Within-subject Change in Average Daily Pain Score From the Baseline Week to Visit 3	Baseline week, Visit 3	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline.
Within-subject Change in Average Daily Pain Score From the Baseline Week to Visit 4	Baseline week, Visit 4	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline.
Within-subject Change in Average Daily Pain Score From the Baseline Week to Visit 5	Baseline week, Visit 5	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline.
Within-subject Change in Average Daily Pain Score From the Baseline Week to Visit 6	Baseline week, Visit 6	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline.
Within-subject Change in Average Daily Pain Score From the Baseline Week to Visit 8	Baseline week, Visit 8	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline.
Within-subject Change in Average Daily Pain Score From the Baseline Week to the Titration Phase	Titration Phase (4 weeks), compared to the Baseline Week	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the titration phase and the average of the Baseline Week.
Within-subject Change in Average Daily Pain Score From the Baseline Week to the Maintenance Phase	Maintenance Phase (12 weeks), compared to the Baseline Week	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the maintenance phase and the average of the Baseline Week.
Within-subject Change in Average Daily Pain Score From the Baseline Week to the Treatment Phase	Treatment Phase (16 weeks), compared to the Baseline Week	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the treatment phase and the average of the Baseline Week.
Within-subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of Maintenance Phase	Last 4 weeks of Maintenance Phase, compared to the Baseline Week	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.
Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's Sleep	Baseline Week, Visit 3	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2.
Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's Sleep	Baseline Week, Visit 4	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2.
Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's Sleep	Baseline Week, Visit 5	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2.
Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's Sleep	Baseline Week, Visit 6	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2.
Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's Sleep	Baseline Week, Visit 7	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2.
Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's Sleep	Baseline Week, Visit 8	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2.
Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's Sleep	Titration Phase (4 weeks), compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the titration phase and the average of the Baseline Week.
Within-subject Change in Average Daily Pain Score From the Baseline Week to Visit 7	Baseline week, Visit 7	An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's Sleep	Treatment Phase (16 weeks), compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement in symptoms. A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the treatment phase and the average of the Baseline Week.
Within-subject Change From the Baseline Week to the Last 4 Weeks of Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	Last 4 weeks of Maintenance Phase, compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.
Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's General Activity	Baseline Week, Visit 3	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's General Activity	Baseline Week, Visit 4	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's General Activity	Baseline Week, Visit 5	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's General Activity	Baseline Week, Visit 6	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's General Activity	Baseline Week, Visit 7	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's General Activity	Baseline Week, Visit 8	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline.
Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's General Activity	Titration Phase (4 weeks), compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the titration phase and the average of the Baseline Week.
Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	Maintenance Phase (12 weeks), compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the maintenance phase and the average of the Baseline Week.
Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's General Activity	Treatment Phase (16 weeks), compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the treatment phase and the average of the Baseline Week.
Within-subject Change From the Baseline Week to the Last 4 Weeks of the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	Last 4 weeks of Maintenance Phase, compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.
Percentage of Days of Rescue Medication Use During the Treatment Phase	During the Treatment Phase (up to 16 weeks)	Percentage of days of rescue medication use was the number of days in the visit/trial phase with rescue medication use divided by the total number of days in the visit/trial phase times 100.
Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Baseline, Visit 8	Quality of life was analyzed using the Short Form-36 (SF-36) Health Survey. The SF-36 is a participant self-rated questionnaire which consists of 8 sub-scores ranging from 0-100 with higher scores indicating a better health state. The sub-scores are: 1. Physical Functioning, 2. Role-Physical, 3. Bodily Pain, 4. General Health, 5. Vitality, 6. Social Functioning, 7. Role-Emotional, 8. Mental Health. Items 1-4 contribute to the physical component Summary (PCS) score. Items 5-8 contribute to the mental component summary (MCS) score. The PCS and MCS were based on the standardized values of the 8 domains. The maximum and minimum possible values for PCS and MCS is 0-100, where higher scores indicate good condition. A positive change value indicates improvement from baseline. As pre-specified in SAP, values were planned to be summarized and disclosed by placebo and LCM 400 mg/day (pooled) groups.
Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Visit 8	The PGIC is a 7-point categorical rating scale in which the subject rates the change in his/her pain since starting trial medication. Categories are as following: much worse, moderately worse, mildly worse, no change, mildly better, moderately better, much better. As pre-specified in SAP, values were planned to be summarized and disclosed by placebo and LCM 400 mg/day (pooled) reporting groups.
Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Visit 8	Categories of satisfaction are as following: very satisfied, satisfied, neither satisfied/dissatisfied, dissatisfied, very dissatisfied, not applicable, not done (no data available).
Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Baseline, Visit 8	The MOS Sleep scale is used to assess the subject's quality of sleep. The scale consists of 12 individual items categorized into two sleep problems indices (SPI I/II) and 5 subscales: sleep disturbance, sleep somnolence, snoring, short of breath (SoB) or headache, sleep adequacy. Scores range from 0 to 100. Sleep adequacy scale: High values indicate a high quality of sleep. A positive change indicates improvement in quality of sleep. All other Sleep Scales: Low values indicate a high quality of sleep. A negative change indicates improvement in quality of sleep.
Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	Maintenance Phase (12 weeks), compared to the Baseline Week	An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the maintenance phase and the average of the Baseline Week.

Countries

Germany

Participant flow

Recruitment details

The study started to enroll patients in June 2006 and concluded in June 2007.

Pre-assignment details

Participant Flow refers to the Randomized Set. The 16-week Treatment Phase consisted of 4-week Titration Phase and 12-week Maintenance Phase.

Participants by arm

Arm	Count
Placebo Subjects underwent sham titration for the entire Titration Phase. All subjects completing the Titration Phase enter a 12-week Maintenance Phase.	179
Lacosamide FT Subjects receive 200 mg/day LCM for the first 3 days, 300 mg/day for the next 4 days, and reach their target dose of 400 mg/day after 1 week. They undergo sham titration for the remaining 3 weeks of the Titration Phase. All subjects completing the Titration Phase enter a 12-week Maintenance Phase.	190
Lacosamide ST Subjects had their dose titrated from 100 mg/day to 400 mg/day at weekly intervals of 100mg. Subjects in this treatment group reach their target dose of 400 mg/day 3 weeks after Visit 2. All subjects completing the Titration Phase enter a 12-week Maintenance Phase.	182
Total Title	551
Total	1,102

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	12	29	17
Overall Study	Exclusion criteria met	0	0	1
Overall Study	Investigator´s decision	1	1	0
Overall Study	Lack of Efficacy	5	1	3
Overall Study	Lost, Reason unknown	1	1	0
Overall Study	Need for prohibited medication	1	0	0
Overall Study	Patient relocated	0	0	1
Overall Study	Patient stopped feeling pain	1	0	0
Overall Study	Personal reasons	0	0	1
Overall Study	PR greater than 250ms	0	0	1
Overall Study	Protocol Violation	0	0	1
Overall Study	Randomization mistake	0	1	1
Overall Study	Sponsor mistake	1	0	0
Overall Study	Sponsor´s decision	0	1	0
Overall Study	Unsatisfactory Compliance	2	2	1
Overall Study	Withdrawal by Subject	6	6	8
Overall Study	Wrong calculation of QT interval	0	0	1

Baseline characteristics

Characteristic	Placebo	Lacosamide FT	Lacosamide ST	Total Title
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	37 Participants	43 Participants	48 Participants	128 Participants
Age, Categorical Between 18 and 65 years	142 Participants	147 Participants	134 Participants	423 Participants
Age, Continuous	56.6 years STANDARD_DEVIATION 9.45	58.0 years STANDARD_DEVIATION 9.46	57.4 years STANDARD_DEVIATION 10.14	57.3 years STANDARD_DEVIATION 9.68
Sex: Female, Male Female	86 Participants	98 Participants	88 Participants	272 Participants
Sex: Female, Male Male	93 Participants	92 Participants	94 Participants	279 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 179	0 / 370
other Total, other adverse events	21 / 179	82 / 370
serious Total, serious adverse events	14 / 179	28 / 370

Outcome results

Primary

Change in Average Daily Pain Score From Baseline Week to the Last 4 Weeks of the Maintenance Phase

An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.

Time frame: Last 4 weeks of Maintenance Phase, compared to the Baseline Week

Population: Only subjects with available data for subject's average daily pain scores are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Change in Average Daily Pain Score From Baseline Week to the Last 4 Weeks of the Maintenance Phase	-1.9 units on a scale	Standard Deviation 2.2
Lacosamide FT	Change in Average Daily Pain Score From Baseline Week to the Last 4 Weeks of the Maintenance Phase	-2.2 units on a scale	Standard Deviation 2.05
Lacosamide ST	Change in Average Daily Pain Score From Baseline Week to the Last 4 Weeks of the Maintenance Phase	-2.4 units on a scale	Standard Deviation 2.08

Comparison: Last Observation Carried Forward (LOCF) procedure was applied for missing daily diary entries between start of trial medication and Visit 8 or last intake of trial medication in the case of discontinuation during the Titration or Maintenance Phase.p-value: =0.04195% CI: [-0.88, -0.02]ANCOVA

Secondary

Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8

The MOS Sleep scale is used to assess the subject's quality of sleep. The scale consists of 12 individual items categorized into two sleep problems indices (SPI I/II) and 5 subscales: sleep disturbance, sleep somnolence, snoring, short of breath (SoB) or headache, sleep adequacy. Scores range from 0 to 100. Sleep adequacy scale: High values indicate a high quality of sleep. A positive change indicates improvement in quality of sleep. All other Sleep Scales: Low values indicate a high quality of sleep. A negative change indicates improvement in quality of sleep.

Time frame: Baseline, Visit 8

Population: 177 subjects treated with Placebo, 188 subjects treated with Lacosamide FT and 177 subjects treated with Lacosamide ST were initially included in the FAS. Only subjects with available data for change from Baseline to Visit 8 in MOS sleep scale scores are included in the analysis. Number of subjects analyzed is given separately per sub-score.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Somnolence	-7.0 units on a scale	Standard Deviation 16.25
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Adequacy	7.2 units on a scale	Standard Deviation 26.11
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SoB/ Headache	-6.7 units on a scale	Standard Deviation 23.32
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Disturbance	-13.4 units on a scale	Standard Deviation 19.3
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SPI II	-10.6 units on a scale	Standard Deviation 14.18
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SPI I	-10.3 units on a scale	Standard Deviation 15.15
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Snoring	-2.7 units on a scale	Standard Deviation 27.33
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SoB/ Headache	-1.0 units on a scale	Standard Deviation 26.75
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Disturbance	-15.2 units on a scale	Standard Deviation 22.65
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Somnolence	-2.1 units on a scale	Standard Deviation 19.69
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Snoring	0.0 units on a scale	Standard Deviation 25.13
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Adequacy	10.3 units on a scale	Standard Deviation 26.37
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SPI I	-8.3 units on a scale	Standard Deviation 17.39
Lacosamide FT	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SPI II	-9.9 units on a scale	Standard Deviation 16.66
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Adequacy	15.1 units on a scale	Standard Deviation 30.28
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Somnolence	-4.6 units on a scale	Standard Deviation 20.41
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SPI II	-13.1 units on a scale	Standard Deviation 19.17
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SPI I	-12.2 units on a scale	Standard Deviation 19.58
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	SoB/ Headache	-7.5 units on a scale	Standard Deviation 24.76
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Snoring	-6.7 units on a scale	Standard Deviation 27.25
Lacosamide ST	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores at Visit 8	Sleep Disturbance	-17.1 units on a scale	Standard Deviation 23.97

Secondary

Percentage of Days of Rescue Medication Use During the Treatment Phase

Percentage of days of rescue medication use was the number of days in the visit/trial phase with rescue medication use divided by the total number of days in the visit/trial phase times 100.

Time frame: During the Treatment Phase (up to 16 weeks)

Population: Only subjects with available data for rescue medication use are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Percentage of Days of Rescue Medication Use During the Treatment Phase	6.6 percentage of days	Standard Deviation 20.27
Lacosamide FT	Percentage of Days of Rescue Medication Use During the Treatment Phase	7.0 percentage of days	Standard Deviation 20.28
Lacosamide ST	Percentage of Days of Rescue Medication Use During the Treatment Phase	9.1 percentage of days	Standard Deviation 23.67

Secondary

Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8

The PGIC is a 7-point categorical rating scale in which the subject rates the change in his/her pain since starting trial medication. Categories are as following: much worse, moderately worse, mildly worse, no change, mildly better, moderately better, much better. As pre-specified in SAP, values were planned to be summarized and disclosed by placebo and LCM 400 mg/day (pooled) reporting groups.

Time frame: Visit 8

Population: Only subjects with available data for Patient's Global Impression of Change in Pain are included in the analysis.

Arm	Measure	Group	Value (NUMBER)
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Mildly worse	3.5 percentage of participants
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Mildly better	31.6 percentage of participants
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Moderately worse	1.2 percentage of participants
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Moderately better	26.9 percentage of participants
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	No change	23.4 percentage of participants
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Much better	12.3 percentage of participants
Placebo	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Much worse	1.2 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Much better	21.6 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Much worse	0.6 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Moderately worse	1.7 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Mildly worse	2.6 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	No change	17.8 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Mildly better	23.3 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Patient's Global Impression of Change in Pain (PGIC) at Visit 8	Moderately better	32.4 percentage of participants

Secondary

Percentage of Patients With Categorized Satisfaction With Medications at Visit 8

Categories of satisfaction are as following: very satisfied, satisfied, neither satisfied/dissatisfied, dissatisfied, very dissatisfied, not applicable, not done (no data available).

Time frame: Visit 8

Population: Only subjects with available data for satisfaction with medications are included in the analysis.

Arm	Measure	Group	Value (NUMBER)
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Satisfied	43.9 percentage of participants
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Very Dissatisfied	4.1 percentage of participants
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Dissatisfied	11.7 percentage of participants
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Very Satisfied	11.7 percentage of participants
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Not Done	2.9 percentage of participants
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Not Applicable	0 percentage of participants
Placebo	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Neither Satisfied/Dissatisfied	25.7 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Dissatisfied	11.8 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Very Satisfied	14.0 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Satisfied	45.5 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Neither Satisfied/Dissatisfied	24.2 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Very Dissatisfied	2.8 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Not Applicable	0.6 percentage of participants
Lacosamide FT	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Not Done	1.1 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Very Dissatisfied	0.6 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Satisfied	50.0 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Not Done	1.8 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Not Applicable	0 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Dissatisfied	8.3 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Neither Satisfied/Dissatisfied	23.8 percentage of participants
Lacosamide ST	Percentage of Patients With Categorized Satisfaction With Medications at Visit 8	Very Satisfied	15.5 percentage of participants

Secondary

Percentage of Subjects With >= 30% or >= 2-point Reduction of with-in Subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of the Maintenance Phase

Time frame: Baseline week, last 4 weeks of the Maintenance Phase

Population: Only subjects with available data for subject's average daily pain scores are included in the analysis.

Arm	Measure	Value (NUMBER)
Placebo	Percentage of Subjects With >= 30% or >= 2-point Reduction of with-in Subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of the Maintenance Phase	50.3 percentage of participants
Lacosamide FT	Percentage of Subjects With >= 30% or >= 2-point Reduction of with-in Subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of the Maintenance Phase	56.4 percentage of participants
Lacosamide ST	Percentage of Subjects With >= 30% or >= 2-point Reduction of with-in Subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of the Maintenance Phase	55.4 percentage of participants

Secondary

Time to Sustainable Pain Relief

Time to sustainable pain relief was defined as the time from Baseline to the first day on which there was a ≥1-point improvement over Baseline in the Likert pain score for those subjects for whom there was also ≥30% reduction in average daily pain score over the last 28 days of the Maintenance Phase as compared to Baseline.

Time frame: From start of trial medication intake (Week 0) up to the last 4 weeks of the Maintenance Phase

Population: Only subjects with available data for subject's average daily pain scores are included in the analysis.

Arm	Measure	Value (MEDIAN)
Placebo	Time to Sustainable Pain Relief	31.0 days
Lacosamide FT	Time to Sustainable Pain Relief	11.0 days
Lacosamide ST	Time to Sustainable Pain Relief	10.0 days

Secondary

Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life

Quality of life was analyzed using the Short Form-36 (SF-36) Health Survey. The SF-36 is a participant self-rated questionnaire which consists of 8 sub-scores ranging from 0-100 with higher scores indicating a better health state. The sub-scores are: 1. Physical Functioning, 2. Role-Physical, 3. Bodily Pain, 4. General Health, 5. Vitality, 6. Social Functioning, 7. Role-Emotional, 8. Mental Health. Items 1-4 contribute to the physical component Summary (PCS) score. Items 5-8 contribute to the mental component summary (MCS) score. The PCS and MCS were based on the standardized values of the 8 domains. The maximum and minimum possible values for PCS and MCS is 0-100, where higher scores indicate good condition. A positive change value indicates improvement from baseline. As pre-specified in SAP, values were planned to be summarized and disclosed by placebo and LCM 400 mg/day (pooled) groups.

Time frame: Baseline, Visit 8

Population: A total of 177 subjects treated with Placebo and 365 subjects treated with lacosamide were initially included in the Full Analysis Set. Only subjects with available data for change from Baseline to Visit 8 in the sub-scores of subject's quality of life are included in the analysis. Number of subjects analyzed is given separately per sub-score.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Bodily Pain	13.4 units on a scale	Standard Deviation 20.51
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Role-Physical	15.3 units on a scale	Standard Deviation 37.8
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Role-Emotional	6.5 units on a scale	Standard Deviation 44.42
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	General Health	5.0 units on a scale	Standard Deviation 15.09
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Mental Health	3.5 units on a scale	Standard Deviation 16.97
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Physical Functioning	3.8 units on a scale	Standard Deviation 16.3
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	PCS	3.9 units on a scale	Standard Deviation 6.61
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Vitality	4.4 units on a scale	Standard Deviation 16.12
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	MCS	1.9 units on a scale	Standard Deviation 10.06
Placebo	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Social Functioning	8.4 units on a scale	Standard Deviation 23.05
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	MCS	1.8 units on a scale	Standard Deviation 10.91
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Physical Functioning	4.4 units on a scale	Standard Deviation 18.85
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Role-Physical	10.3 units on a scale	Standard Deviation 39.33
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Bodily Pain	16.9 units on a scale	Standard Deviation 19.99
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	General Health	4.8 units on a scale	Standard Deviation 15.39
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Vitality	7.5 units on a scale	Standard Deviation 17.94
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Social Functioning	5.1 units on a scale	Standard Deviation 22.37
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Role-Emotional	4.7 units on a scale	Standard Deviation 47.28
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	Mental Health	4.8 units on a scale	Standard Deviation 18.6
Lacosamide FT	Within-subject Change From Baseline to Visit 8 in Subject's Quality of Life	PCS	4.0 units on a scale	Standard Deviation 6.99

Secondary

Within-subject Change From the Baseline Week to the Last 4 Weeks of Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep

An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.

Time frame: Last 4 weeks of Maintenance Phase, compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Last 4 Weeks of Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	-1.9 units on a scale	Standard Deviation 2.3
Lacosamide FT	Within-subject Change From the Baseline Week to the Last 4 Weeks of Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	-2.1 units on a scale	Standard Deviation 2.24
Lacosamide ST	Within-subject Change From the Baseline Week to the Last 4 Weeks of Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	-2.3 units on a scale	Standard Deviation 2.37

Secondary

Within-subject Change From the Baseline Week to the Last 4 Weeks of the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity

An 11-point Likert scale was used to assess the subject's general activity. The subject rated how the pain had interfered with general activity over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.

Time frame: Last 4 weeks of Maintenance Phase, compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Last 4 Weeks of the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.9 units on a scale	Standard Deviation 2.3
Lacosamide FT	Within-subject Change From the Baseline Week to the Last 4 Weeks of the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	-2.1 units on a scale	Standard Deviation 2.16
Lacosamide ST	Within-subject Change From the Baseline Week to the Last 4 Weeks of the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	-2.2 units on a scale	Standard Deviation 2.38

Secondary

Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Maintenance Phase (12 weeks), compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	-2.0 units on a scale	Standard Deviation 2.17
Lacosamide FT	Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	-2.2 units on a scale	Standard Deviation 2.05
Lacosamide ST	Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's General Activity	-2.2 units on a scale	Standard Deviation 2.27

Secondary

Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep

An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the maintenance phase and the average of the Baseline Week.

Time frame: Maintenance Phase (12 weeks), compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	-2.0 units on a scale	Standard Deviation 2.15
Lacosamide FT	Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	-2.2 units on a scale	Standard Deviation 2.22
Lacosamide ST	Within-subject Change From the Baseline Week to the Maintenance Phase in Daily Perception of Pain Interference With Subject's Sleep	-2.4 units on a scale	Standard Deviation 2.24

Secondary

Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Titration Phase (4 weeks), compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.0 units on a scale	Standard Deviation 1.5
Lacosamide FT	Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.2 units on a scale	Standard Deviation 1.6
Lacosamide ST	Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.3 units on a scale	Standard Deviation 1.72

Secondary

Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's Sleep

An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the titration phase and the average of the Baseline Week.

Time frame: Titration Phase (4 weeks), compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's Sleep	-1.0 units on a scale	Standard Deviation 1.54
Lacosamide FT	Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's Sleep	-1.3 units on a scale	Standard Deviation 1.62
Lacosamide ST	Within-subject Change From the Baseline Week to the Titration Phase in Daily Perception of Pain Interference With Subject's Sleep	-1.3 units on a scale	Standard Deviation 1.67

Secondary

Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Treatment Phase (16 weeks), compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.6 units on a scale	Standard Deviation 1.94
Lacosamide FT	Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.8 units on a scale	Standard Deviation 1.85
Lacosamide ST	Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's General Activity	-1.9 units on a scale	Standard Deviation 2.06

Secondary

Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's Sleep

An 11-point Likert scale was used to assess the subject's sleep. The subject rated how the pain had interfered with sleep over the past 12 hours, from 0 (no interference) to 10 (complete interference). A negative value indicates improvement in symptoms. A lower value on the scale indicates improvement in symptoms. A negative change value indicates improvement from Baseline. Baseline Week was defined as the average of pain interference scores at the last 7 days prior to Visit 2. The value reported below is calculated as a difference between the average of the treatment phase and the average of the Baseline Week.

Time frame: Treatment Phase (16 weeks), compared to the Baseline Week

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's Sleep	-1.6 units on a scale	Standard Deviation 1.94
Lacosamide FT	Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's Sleep	-1.8 units on a scale	Standard Deviation 1.94
Lacosamide ST	Within-subject Change From the Baseline Week to the Treatment Phase in Daily Perception of Pain Interference With Subject's Sleep	-2.0 units on a scale	Standard Deviation 2.04

Secondary

Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Baseline Week, Visit 3

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's General Activity	-0.6 units on a scale	Standard Deviation 1.3
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's General Activity	-0.7 units on a scale	Standard Deviation 1.26
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's General Activity	-0.7 units on a scale	Standard Deviation 1.4

Secondary

Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's Sleep

Time frame: Baseline Week, Visit 3

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's Sleep	-0.5 units on a scale	Standard Deviation 1.27
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's Sleep	-0.7 units on a scale	Standard Deviation 1.26
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 3 in Daily Perception of Pain Interference With Subject's Sleep	-0.6 units on a scale	Standard Deviation 1.35

Secondary

Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Baseline Week, Visit 4

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's General Activity	-1.0 units on a scale	Standard Deviation 1.57
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's General Activity	-1.3 units on a scale	Standard Deviation 1.7
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's General Activity	-1.3 units on a scale	Standard Deviation 1.84

Secondary

Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's Sleep

Time frame: Baseline Week, Visit 4

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's Sleep	-0.9 units on a scale	Standard Deviation 1.72
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's Sleep	-1.3 units on a scale	Standard Deviation 1.69
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 4 in Daily Perception of Pain Interference With Subject's Sleep	-1.3 units on a scale	Standard Deviation 1.83

Secondary

Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Baseline Week, Visit 5

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's General Activity	-1.4 units on a scale	Standard Deviation 1.83
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's General Activity	-1.6 units on a scale	Standard Deviation 2.01
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's General Activity	-1.8 units on a scale	Standard Deviation 2.11

Secondary

Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's Sleep

Time frame: Baseline Week, Visit 5

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's Sleep	-1.4 units on a scale	Standard Deviation 1.87
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's Sleep	-1.7 units on a scale	Standard Deviation 2.04
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 5 in Daily Perception of Pain Interference With Subject's Sleep	-1.8 units on a scale	Standard Deviation 2.01

Secondary

Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Baseline Week, Visit 6

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's General Activity	-1.9 units on a scale	Standard Deviation 2.15
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's General Activity	-2.0 units on a scale	Standard Deviation 2.12
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's General Activity	-2.1 units on a scale	Standard Deviation 2.28

Secondary

Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's Sleep

Time frame: Baseline Week, Visit 6

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's Sleep	-1.9 units on a scale	Standard Deviation 2.15
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's Sleep	-2.0 units on a scale	Standard Deviation 2.28
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 6 in Daily Perception of Pain Interference With Subject's Sleep	-2.2 units on a scale	Standard Deviation 2.26

Secondary

Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Baseline Week, Visit 7

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's General Activity	-2.2 units on a scale	Standard Deviation 2.24
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's General Activity	-2.3 units on a scale	Standard Deviation 2.11
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's General Activity	-2.3 units on a scale	Standard Deviation 2.37

Secondary

Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's Sleep

Time frame: Baseline Week, Visit 7

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's Sleep	-2.2 units on a scale	Standard Deviation 2.19
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's Sleep	-2.3 units on a scale	Standard Deviation 2.22
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 7 in Daily Perception of Pain Interference With Subject's Sleep	-2.5 units on a scale	Standard Deviation 2.37

Secondary

Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's General Activity

Time frame: Baseline Week, Visit 8

Population: Only subjects with available data for subject's pain interference with subject's general activity at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's General Activity	-2.1 units on a scale	Standard Deviation 2.29
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's General Activity	-2.4 units on a scale	Standard Deviation 2.15
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's General Activity	-2.4 units on a scale	Standard Deviation 2.42

Secondary

Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's Sleep

Time frame: Baseline Week, Visit 8

Population: Only subjects with available data for subject's pain interference with subject's sleep at the respective are included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's Sleep	-2.1 units on a scale	Standard Deviation 2.28
Lacosamide FT	Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's Sleep	-2.5 units on a scale	Standard Deviation 2.26
Lacosamide ST	Within-subject Change From the Baseline Week to Visit 8 in Daily Perception of Pain Interference With Subject's Sleep	-2.5 units on a scale	Standard Deviation 2.38

Secondary

Within-subject Change in Average Daily Pain Score From the Baseline Week to the Last 4 Weeks of Maintenance Phase

An 11-point Likert scale is used to assess the subject's average daily pain. This scale is completed by the subject twice daily (once in the morning and once in the evening). The subject rates his/her average pain over the last 12 hours, from 0 (no pain) to 10 (worst pain ever experienced). The daily pain score is defined as the average score of those collected in the morning and evening. A negative value indicates improvement from Baseline. The value reported below is calculated as a difference between the average of the last available 28 days of maintenance for participants completing the maintenance phase (or the last 28 days prior to discontinuation for participants who discontinued in the titration or maintenance phase) and the average of the Baseline week.

Time frame: Last 4 weeks of Maintenance Phase, compared to the Baseline Week