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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
551
* Pharmaceutical form: Immediate release film-coated tablets * Concentration: 50mg/ 100mg * Route of administration: Oral use
* Pharmaceutical form: Immediate release film-coated tablets * Route of administration: Oral use
Unnamed facility
Monheim, Germany
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
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
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
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.
Time frame: Baseline week, last 4 weeks of the Maintenance Phase
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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.
Time frame: Baseline week, Visit 3
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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.
Time frame: Baseline week, Visit 4
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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.
Time frame: Baseline week, Visit 5
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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.
Time frame: Baseline week, Visit 6
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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.
Time frame: Baseline week, Visit 7
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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.
Time frame: Baseline week, Visit 8
Within-subject Change in Average Daily Pain Score From the Baseline Week to the Titration 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 titration phase and the average of the Baseline Week.
Time frame: Titration Phase (4 weeks), compared to the Baseline Week
Within-subject Change in Average Daily Pain Score From the Baseline Week to 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. 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.
Time frame: Maintenance Phase (12 weeks), compared to the Baseline Week
Within-subject Change in Average Daily Pain Score From the Baseline Week to the Treatment 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 treatment phase and the average of the Baseline Week.
Time frame: Treatment Phase (16 weeks), compared to the Baseline Week
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
Within-subject Change From the Baseline Week to Visit 3 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.
Time frame: Baseline Week, Visit 3
Within-subject Change From the Baseline Week to Visit 4 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.
Time frame: Baseline Week, Visit 4
Within-subject Change From the Baseline Week to Visit 5 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.
Time frame: Baseline Week, Visit 5
Within-subject Change From the Baseline Week to Visit 6 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.
Time frame: Baseline Week, Visit 6
Within-subject Change From the Baseline Week to Visit 7 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.
Time frame: Baseline Week, Visit 7
Within-subject Change From the Baseline Week to Visit 8 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.
Time frame: Baseline Week, Visit 8
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
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
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
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
Within-subject Change From the Baseline Week to Visit 3 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.
Time frame: Baseline Week, Visit 3
Within-subject Change From the Baseline Week to Visit 4 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.
Time frame: Baseline Week, Visit 4
Within-subject Change From the Baseline Week to Visit 5 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.
Time frame: Baseline Week, Visit 5
Within-subject Change From the Baseline Week to Visit 6 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.
Time frame: Baseline Week, Visit 6
Within-subject Change From the Baseline Week to Visit 7 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.
Time frame: Baseline Week, Visit 7
Within-subject Change From the Baseline Week to Visit 8 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.
Time frame: Baseline Week, Visit 8
Within-subject Change From the Baseline Week to the Titration 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 titration phase and the average of the Baseline Week.
Time frame: Titration Phase (4 weeks), compared to 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
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.
Time frame: Maintenance Phase (12 weeks), compared to 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
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.
Time frame: Treatment Phase (16 weeks), compared to 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
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
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)
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
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
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
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
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