A Follow-On Trial to Assess the Long Term Safety and Efficacy of SPM 927 in Painful Distal Diabetic Neuropathy

Study Overview
=================
Brief Summary
-----------------
Phase 2/3 open-label trial to assess the safety and tolerability of long-term treatment with lacosamide (SPM 927) in subjects with painful diabetic neuropathy. The safety and tolerability of the different doses of lacosamide will be investigated.

Detailed Description
-----------------
This phase 2/3 open-label trial is being conducted at approximately 100 sites in the US to assess the safety and tolerability of long-term treatment with lacosamide (SPM 927) in subjects with painful diabetic neuropathy. Approximately 525 subjects will be enrolled. To qualify for this trial, subjects with symptoms of painful distal diabetic neuropathy ranging in duration from 6 months to 5 years must have completed trials SP665, SP742, or SP768 and, in the investigator's opinion, may benefit from long-term administration of lacosamide. Subjects will be titrated to their optimal dose of lacosamide (up to 600mg/day). The safety and tolerability of the different doses of lacosamide will be investigated throughout the trial. In addition, to determine what effect lacosamide has on diabetic neuropathic pain, subjects will use a diary to record their daily pain intensity and pain interference with sleep and activity. Subjects' quality of life will also be investigated.

Official Title
-----------------
A Multi-Center, Open-Label, Follow-On Trial to Assess the Long Term Safety and Efficacy of SPM 927 in Subjects With Painful Distal Diabetic Neuropathy

Conditions
-----------------
Diabetic Neuropathy

Intervention / Treatment
-----------------
* Drug: lacosamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who completed Study SP665, SP742, or SP768 and, in the investigators opinion, might benefit from long-term administration of SPM 927. Exception: subjects who prematurely discontinued Study SP742 or SP768 due to lack of efficacy or due to intolerability to trial medication may be eligible to participate in Study SP745, after consultation with the medical monitor. Exclusion Criteria: Subject has clinically relevant electrocardiogram (ECG) abnormalities, or QT-corrected (QTc) interval >=500 milliseconds (ms), and/or a QTc interval increase of >=60ms from the mean pre-dose QTc value at Visit 2 of Studies SP665, SP742 or SP768. Subject has aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >=3 times the upper limit of the normal range (ULN) with total bilirubin >=2 times ULN or transaminases (AST and/or ALT) >=5 times ULN. Subject has a clinically relevant medical condition that, in the opinion of the investigator, jeopardizes or compromises the subject's ability to participate in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 32 Years
Maximum Age: 81 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day | Drug: lacosamide<br>* Open-label treatment (two times per day) with film-coated tablets include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, and 600mg/day throughout individual study period.<br>* Other names: SPM927;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Events (AEs) Reported Spontaneously by the Subject or Observed by the Investigator. | Number of subjects with adverse events (AEs) reported spontaneously by the subject or observed by the investigator (serious and non-serious). | Throughout the study up to a maximum study period of 2.8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Daily Pain Score Using an 11-point Likert Scale (0-10). | Change from Baseline in average daily pain score using an 11-point Likert scale (0-10). On Likert scale, 0=no pain and 10=worst possible pain. | Baseline to end of entire treatment phase (maximum study period of 2.8 years). | 
| Change From Baseline in Average Pain Score as Measured by a 100mm Visual Analogue Scale (VAS). | Change from Baseline in average pain score as measured by a 100mm Visual Analogue Scale (VAS). On VAS 0mm=no pain and 100mm=worst possible pain. | Baseline to end of entire treatment phase (maximum study period of 2.8 years). | 
| Patient's Global Impression of Change (PGIC) From Baseline in Pain. | Patient's Global Impression of Change (PGIC) from Baseline in Pain. Original categorical responses are much worse, moderately worse, mildly worst, no change, mildly better, moderately better, and much better. Reported results are presented as Better (sum of mildly, moderately, or much better), No Change, or Worse (sum of mildly, moderately, or much worse). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Intensity. | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) for intensity of pain where 0=no pain and 10=most intense pain sensation imaginable. | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Sharpness | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) for sharpness of pain where 0=not sharp and 10=most sharp sensation imaginable (like a knife). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Heat | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with heat sensation where 0=not hot and 10=the most hot sensation imaginable (on fire). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Dullness | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with dullness of pain where 0=not dull and 10=most dull sensation imaginable. | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Cold | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with cold sensation where 0=not cold and 10=most cold sensation imaginable (freezing). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Sensitivity | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with sensitivity of pain where 0=not sensitive and 10=most sensitive sensation imaginable (raw skin). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Itchiness | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with itchiness where 0=not itchy and 10=most itchy sensation imaginable (like poison oak). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Unpleasantness | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with unpleasantness where 0=not pleasant and 10=most unpleasant sensation imaginable (intolerable). | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Deep Pain | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with deep pain where 0=no deep pain and 10=most intense deep pain sensation imaginable. | Baseline to Termination Visit | 
| Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Surface Pain | Within-subject change in neuropathic pain using the Neuropathic Pain Scale (NPS) with surface pain where 0=no surface pain and 10=most intense surface pain imaginable. | Baseline to Termination Visit | 
| Change From Baseline in Average Pain Interference With Sleep (11-point Likert Scale) | Change from Baseline in average pain interference with sleep (11-point Likert scale) where 0=no interference with sleep and 10=worst possible interference with sleep. | Baseline to end of entire treatment phase visit | 
| Change From Baseline in Average Pain Interference With Activity (11-point Likert Scale) | Change from Baseline in average pain interference with activity (11-point Likert scale) where 0=no interfence with activity and 10=worst possible interference with activity. | Baseline to end of entire treatment phase visit | 
| Change From Baseline in Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) | Change from Baseline in quality of life using the SF-36 Health Survey - Physical Component Summary (PCS). Values range from 0 to 100 with high values indicating a good condition. Positive change in baseline values indicate improvement in quality of life. | Baseline to Termination Visit | 
| Change From Baseline in Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) | Change from Baseline in quality of life using the SF-36 Health Survey - Mental Component Summary (MCS). Values range from 0 to 100 with high values indicating a good condition. Positive change in baseline values indicate improvement in quality of life. | Baseline to Termination Visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Painful Distal Diabetic Neuropathy