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

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00235443

Enrollment

451

Registered

2005-10-10

Start date

2004-09-30

Completion date

2008-07-31

Last updated

2018-07-17

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

Conditions

Diabetic Neuropathy

Keywords

Painful Distal Diabetic Neuropathy

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.

Interventions

DRUGlacosamide

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

32 Years to 81 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change From Baseline in Average Pain Score as Measured by a 100mm Visual Analogue Scale (VAS).	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). On VAS 0mm=no pain and 100mm=worst possible pain.
Patient's Global Impression of Change (PGIC) From Baseline in Pain.	Baseline to Termination Visit	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).
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Intensity.	Baseline to Termination Visit	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.
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Sharpness	Baseline to Termination Visit	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).
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Heat	Baseline to Termination Visit	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).
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Dullness	Baseline to Termination Visit	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.
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Cold	Baseline to Termination Visit	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).
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Sensitivity	Baseline to Termination Visit	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).
Change From Baseline in Average Daily Pain Score Using an 11-point Likert Scale (0-10).	Baseline to end of entire treatment phase (maximum study period of 2.8 years).	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.
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Unpleasantness	Baseline to Termination Visit	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).
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Deep Pain	Baseline to Termination Visit	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.
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Surface Pain	Baseline to Termination Visit	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.
Change From Baseline in Average Pain Interference With Sleep (11-point Likert Scale)	Baseline to end of entire treatment phase visit	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.
Change From Baseline in Average Pain Interference With Activity (11-point Likert Scale)	Baseline to end of entire treatment phase visit	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.
Change From Baseline in Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS)	Baseline to Termination Visit	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.
Change From Baseline in Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS)	Baseline to Termination Visit	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.
Within-subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Itchiness	Baseline to Termination Visit	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).

Countries

United States

Participant flow

Recruitment details

Trial SP745 (NCT00235443) was conducted in 93 sites in the US and 89 of these sites screened at least 1 subject. The first subject was enrolled on 13Sep2004 and the last subject completed on 25Jul2008.

Participants by arm

Arm	Count
Lacosamide 100mg/Day Modal dose = Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day	11
Lacosamide 200mg/Day Modal dose = Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day	57
Lacosamide 300mg/Day Modal dose = Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day	85
Lacosamide 400mg/Day Modal dose = Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day	205
Lacosamide 500mg/Day Modal dose = Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day	39
Lacosamide 600mg/Day Modal dose = Open label doses (two times per day) include 100mg/day, 200mg/day, 300mg/day, 400mg/day, 500mg/day, 600mg/day	54
Total	451

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	4	12	17	44	10	15
Overall Study	Lack of Efficacy	0	1	5	12	2	9
Overall Study	Lost to Follow-up	0	8	6	6	4	3
Overall Study	Other reasons for premature termination	1	6	6	7	3	6
Overall Study	Unsatisfactory compliance	0	2	3	4	1	0
Overall Study	Withdrawal by Subject	3	9	25	24	10	12

Baseline characteristics

Characteristic	Lacosamide 200mg/Day	Lacosamide 300mg/Day	Lacosamide 400mg/Day	Lacosamide 100mg/Day	Lacosamide 500mg/Day	Lacosamide 600mg/Day	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	19 Participants	24 Participants	45 Participants	5 Participants	9 Participants	10 Participants	112 Participants
Age, Categorical Between 18 and 65 years	38 Participants	61 Participants	160 Participants	6 Participants	30 Participants	44 Participants	339 Participants
Age, Continuous	59.3 years STANDARD_DEVIATION 10.53	60.5 years STANDARD_DEVIATION 8.55	57.3 years STANDARD_DEVIATION 9.43	64.0 years STANDARD_DEVIATION 8.16	56.9 years STANDARD_DEVIATION 9.52	55.5 years STANDARD_DEVIATION 10.1	58.1 years STANDARD_DEVIATION 9.6
Region of Enrollment United States	57 participants	85 participants	205 participants	11 participants	39 participants	54 participants	451 participants
Sex: Female, Male Female	33 Participants	48 Participants	80 Participants	5 Participants	16 Participants	18 Participants	200 Participants
Sex: Female, Male Male	24 Participants	37 Participants	125 Participants	6 Participants	23 Participants	36 Participants	251 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	10 / 11	47 / 57	68 / 85	183 / 205	28 / 39	43 / 54	379 / 451
serious Total, serious adverse events	1 / 11	13 / 57	17 / 85	52 / 205	10 / 39	7 / 54	100 / 451

Outcome results

Primary

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).

Time frame: Throughout the study up to a maximum study period of 2.8 years