Study Evaluating Long-term Safety and Efficacy of Lacosamide in Subjects With Painful Distal Diabetic Neuropathy.

A Multi-center, Open-label, follow-on Trial to Assess the Long-term Safety and Efficacy of Lacosamide in Subjects With Painful Distal Diabetic Neuropathy Including a Double-blind, Randomized Time Point Withdrawal Subtrial.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00546351

Enrollment

621

Registered

2007-10-18

Start date

2004-05-31

Completion date

2011-01-31

Last updated

2023-09-21

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

Conditions

Painful Diabetic Neuropathy

Keywords

Lacosamide

Brief summary

SP746 (NCT00546351) is a multi-center, open-label, follow-on trial. The purpose of this trial is to assess safety and tolerability of long-term exposure of lacosamide (previously referred to as SPM 927) in subjects with painful distal diabetic neuropathy.

Interventions

DRUGLacosamide

50 to 100 mg Lacosamide film-coated tablets; two times per day up to 600 mg/day; 6.5 years

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subjects who completed Study SP743 (NCT00238524) or SP874 (NCT00350103) and, in the investigator's opinion, might benefit from long-term administration of SP746 (NCT00546351). Exception: subjects who prematurely discontinued * SP743 (NCT00238524) or SP874 (NCT00350103) due to lack of efficacy or due to intolerability to trial medication (after Visit 5but prior to entering the Maintenance Phase) may be eligible to participate in SP746 (NCT00546351), after consultation with the medical monitor

Exclusion criteria

* Subject has clinically relevant ECG abnormalities, or a QTc interval ≥500 ms, and/or a QTc interval increase of ≥60 ms from the mean pre-dose QTc value at Visit 2 of SP743 (NCT00238524) or SP874 (NCT00350103) * 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 * Subject is a pregnant or nursing female, or is of childbearing potential and is not surgically sterile, 2 years postmenopausal, or does not practice 2 combined methods of contraception

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Experiencing the Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (Approximately 6.5 Years).	From entry Visit 1 through end of treatment (approximately 6.5 years)	Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment.
Number of Participants Experiencing the Occurrence of at Least One Serious Adverse Event (SAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (Approximately 6.5 Years).	From entry Visit 1 through end of treatment (approximately 6.5 years)	A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Is fatal * Is life-threatening * Results in persistent or significant disability/incapacity * Requires inpatient hospitalization * Prolongs existing inpatient hospitalization * Is a congenital anomaly/birth defect * Is considered to be an important medical event. Such an event may not be immediately life threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definitions above

Secondary

Measure	Time frame	Description
Average Daily Pain Score Using an 11-point Likert Scale (0-10) at Last Visit.	Last Visit (approximately 2 years)	On the Likert Scale, 0 = no pain and 10 = worst possible pain.
Average Pain Score as Measured by a 100 mm Visual Analog Scale (VAS) at Baseline.	Baseline	Visual Analog Scale (VAS) 0 mm = no pain and 100 mm = worst possible pain.
Average Pain Score as Measured by a 100 mm Visual Analogue Scale (VAS) at Last Visit.	Last Visit (approximately 2 years)	On VAS 0 mm = no pain and 100 mm = worst possible pain.
Patient's Global Impression of Change (PGIC) at Last Visit.	Last Visit (approximately 2 years)	The PGIC is a 7-point self-administered categorical rating scale in which the subject rated the change in pain since starting trial medication (from much worse \[score of 1\] to much better \[score of 7\]). 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 at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = no pain and 10 = most intense pain sensation imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Sharpness at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not sharp and 10 = most sharp sensation imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Heat at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not hot and 10 = the most hot sensation imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Cold at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not cold and 10 = the coldest sensation imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Dullness at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not dull and 10 = most dull sensation imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Unpleasantness at Final Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not unpleasant and 10 = most unpleasant sensation imaginable.
Average Pain Interference With Activity (11-point Likert Scale) at Last Visit.	Last Visit	0 = no interference with activity and 10 = worst possible interference with activity.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Deep Pain at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = no deep pain and 10 = most intense deep pain imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Itchiness at Final Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not itchy and 10 = most itchy sensation imaginable.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Sensitivity at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = not sensitive and 10 = most sensitive sensation imaginable.
Average Pain Interference With Sleep (11-point Likert Scale) at Baseline.	Baseline	0 = no interference with sleep and 10 = worst possible interference with sleep.
Average Pain Interference With Sleep (11-point Likert Scale) at Last Visit.	Last Visit	0 = no interference with sleep and 10 = worst possible interference with sleep.
Average Pain Interference With Activity (11-point Likert Scale) at Baseline.	Baseline	0 = no interference with activity and 10 = worst possible interference with activity.
Average Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) at Baseline.	Baseline	The SF-36 Health Survey measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS = physical functioning, role-physical, bodily pain, and general health; MCS = vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0 = worst score (or quality of life) and 100 = best score.
Average Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) at Last Visit.	Last Visit	The SF-36 Health Survey measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS = physical functioning, role-physical, bodily pain, and general health; MCS = vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0 = worst score (or quality of life) and 100 = best score.
Average Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) at Baseline.	Baseline	The SF-36 Health Survey measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS = physical functioning, role-physical, bodily pain, and general health; MCS = vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0 = worst score (or quality of life) and 100 = best score.
Average Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) at Last Visit.	Last Visit	The SF-36 Health Survey measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS = physical functioning, role-physical, bodily pain, and general health; MCS = vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0 = worst score (or quality of life) and 100 = best score.
Within-Subject Change in Neuropathic Pain Using the Neuropathic Pain Scale (NPS) - Surface Pain at Last Visit.	Baseline Visit; Last Visit (approximately 2 years)	0 = no surface pain and 10 = most intense surface pain imaginable.
Average Daily Pain Score Using an 11-point Likert Scale (0-10) at Baseline Visit.	Baseline	On the Likert Scale, 0 = no pain and 10 = worst possible pain.

Countries

Austria, Belgium, Bulgaria, Czechia, Finland, France, Germany, Hungary, Italy, Poland, Romania, Russia, Serbia, Spain, United Kingdom

Participant flow

Recruitment details

The study started in May 2004 with subjects from Austria, Belgium, Bulgaria, Czech Republic, Finland, France, Germany, Hungary, Italy, Poland, Romania, Russia, Serbia, Spain, and United Kingdom. The primary completion date occurred in January 2011, with study completion in January 2011.

Pre-assignment details

Participant Flow and Baseline Characteristics refer to the Safety Set (SS).

Participants by arm

Arm	Count
Lacosamide 50 to 100 mg Lacosamide film-coated tablets; two times per day up to 600 mg/day; 6.5 years.	621
Total	621

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	76
Overall Study	Lack of Efficacy	15
Overall Study	Lost to Follow-up	9
Overall Study	Other reasons for premature termination	17
Overall Study	Protocol Deviation	1
Overall Study	Unsatisfactory compliance	9
Overall Study	Withdrawal by Subject	109

Baseline characteristics

Characteristic	Lacosamide
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	121 Participants
Age, Categorical Between 18 and 65 years	500 Participants
Age, Continuous	56.8 years STANDARD_DEVIATION 9.51
Region of Enrollment Austria	9 participants
Region of Enrollment Belgium	19 participants
Region of Enrollment Bulgaria	62 participants
Region of Enrollment Czech Republic	57 participants
Region of Enrollment Finland	1 participants
Region of Enrollment France	6 participants
Region of Enrollment Germany	117 participants
Region of Enrollment Hungary	76 participants
Region of Enrollment Italy	7 participants
Region of Enrollment Poland	101 participants
Region of Enrollment Romania	61 participants
Region of Enrollment Russian Federation	30 participants
Region of Enrollment Serbia	54 participants
Region of Enrollment Spain	2 participants
Region of Enrollment United Kingdom	19 participants
Sex: Female, Male Female	296 Participants
Sex: Female, Male Male	325 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	169 / 621
serious Total, serious adverse events	132 / 621

Outcome results

Primary

Number of Participants Experiencing the Occurrence of at Least One Serious Adverse Event (SAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (Approximately 6.5 Years).

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Is fatal * Is life-threatening * Results in persistent or significant disability/incapacity * Requires inpatient hospitalization * Prolongs existing inpatient hospitalization * Is a congenital anomaly/birth defect * Is considered to be an important medical event. Such an event may not be immediately life threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definitions above

Time frame: From entry Visit 1 through end of treatment (approximately 6.5 years)

Population: This analysis includes all subjects (all 621) in the Safety Set (SS).

Arm	Measure	Value (NUMBER)
Lacosamide	Number of Participants Experiencing the Occurrence of at Least One Serious Adverse Event (SAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (Approximately 6.5 Years).	132 participants

Primary

Number of Participants Experiencing the Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (Approximately 6.5 Years).

Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment.

Time frame: From entry Visit 1 through end of treatment (approximately 6.5 years)

Population: This analysis includes all subjects (all 621) in the Safety Set (SS).

Arm	Measure	Value (NUMBER)
Lacosamide	Number of Participants Experiencing the Occurrence of at Least One Treatment-emergent Adverse Event (TEAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (Approximately 6.5 Years).	416 participants

Secondary

Average Daily Pain Score Using an 11-point Likert Scale (0-10) at Baseline Visit.

On the Likert Scale, 0 = no pain and 10 = worst possible pain.

Time frame: Baseline

Population: Of the 621 subjects in the Safety Set (SS), 620 are included in this analysis.~Data was not available for 1 subject at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Daily Pain Score Using an 11-point Likert Scale (0-10) at Baseline Visit.	6.45 units on a scale	Standard Deviation 1.371

Secondary

Average Daily Pain Score Using an 11-point Likert Scale (0-10) at Last Visit.

On the Likert Scale, 0 = no pain and 10 = worst possible pain.

Time frame: Last Visit (approximately 2 years)

Population: Of the 621 subjects in the Safety Set (SS), 619 are included in this analysis.~Data was not available for 2 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Daily Pain Score Using an 11-point Likert Scale (0-10) at Last Visit.	3.01 units on a scale	Standard Deviation 2.246

Secondary

Average Pain Interference With Activity (11-point Likert Scale) at Baseline.

0 = no interference with activity and 10 = worst possible interference with activity.

Time frame: Baseline

Population: Of the 621 subjects in the Safety Set (SS), 620 are included in this analysis.~Data was not available for 1 subject at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Pain Interference With Activity (11-point Likert Scale) at Baseline.	6.11 units on a scale	Standard Deviation 1.66

Secondary

Average Pain Interference With Activity (11-point Likert Scale) at Last Visit.

0 = no interference with activity and 10 = worst possible interference with activity.

Time frame: Last Visit

Population: Of the 621 subjects in the Safety Set (SS), 619 are included in this analysis.~Data was not available for 2 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Pain Interference With Activity (11-point Likert Scale) at Last Visit.	2.89 units on a scale	Standard Deviation 2.349

Secondary

Average Pain Interference With Sleep (11-point Likert Scale) at Baseline.

0 = no interference with sleep and 10 = worst possible interference with sleep.

Time frame: Baseline

Population: Of the 621 subjects in the Safety Set (SS), 620 are included in this analysis.~Data was not available for 1 subject at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Pain Interference With Sleep (11-point Likert Scale) at Baseline.	5.98 units on a scale	Standard Deviation 1.85

Secondary

Average Pain Interference With Sleep (11-point Likert Scale) at Last Visit.

0 = no interference with sleep and 10 = worst possible interference with sleep.

Time frame: Last Visit

Population: Of the 621 subjects in the Safety Set (SS), 619 are included in this analysis.~Data was not available for 2 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Pain Interference With Sleep (11-point Likert Scale) at Last Visit.	2.73 units on a scale	Standard Deviation 2.281

Secondary

Average Pain Score as Measured by a 100 mm Visual Analog Scale (VAS) at Baseline.

Visual Analog Scale (VAS) 0 mm = no pain and 100 mm = worst possible pain.

Time frame: Baseline

Population: Of the 621 subjects in the Safety Set (SS), 213 are included in this analysis.~Data was not available for 408 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Pain Score as Measured by a 100 mm Visual Analog Scale (VAS) at Baseline.	65.83 units on a scale	Standard Deviation 15.986

Secondary

Average Pain Score as Measured by a 100 mm Visual Analogue Scale (VAS) at Last Visit.

On VAS 0 mm = no pain and 100 mm = worst possible pain.

Time frame: Last Visit (approximately 2 years)

Population: Of the 621 subjects in the Safety Set (SS), 214 are included in this analysis.~Data was not available for 407 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Pain Score as Measured by a 100 mm Visual Analogue Scale (VAS) at Last Visit.	30.47 units on a scale	Standard Deviation 23.94

Secondary

Average Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) at Baseline.

The SF-36 Health Survey measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS = physical functioning, role-physical, bodily pain, and general health; MCS = vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0 = worst score (or quality of life) and 100 = best score.

Time frame: Baseline

Population: Of the 621 subjects in the Safety Set (SS), 588 are included in this analysis.~Data was not available for 33 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) at Baseline.	42.8 units on a scale	Standard Deviation 11.04

Secondary

Average Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) at Last Visit.

Time frame: Last Visit

Population: Of the 621 subjects in the Safety Set (SS), 552 are included in this analysis.~Data was not available for 69 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Quality of Life Using the SF-36 Health Survey - Mental Component Summary (MCS) at Last Visit.	44.5 units on a scale	Standard Deviation 10.9

Secondary

Average Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) at Baseline.

Time frame: Baseline

Population: Of the 621 subjects in the Safety Set (SS), 588 are included in this analysis.~Data was not available for 33 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) at Baseline.	32.8 units on a scale	Standard Deviation 8.04

Secondary

Average Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) at Last Visit.

Time frame: Last Visit

Population: Of the 621 subjects in the Safety Set (SS), 552 are included in this analysis.~Data was not available for 69 subjects at the time of this measurement.

Arm	Measure	Value (MEAN)	Dispersion
Lacosamide	Average Quality of Life Using the SF-36 Health Survey - Physical Component Summary (PCS) at Last Visit.	38.4 units on a scale	Standard Deviation 9.41

Secondary

Patient's Global Impression of Change (PGIC) at Last Visit.

The PGIC is a 7-point self-administered categorical rating scale in which the subject rated the change in pain since starting trial medication (from much worse \[score of 1\] to much better \[score of 7\]). Reported results are presented as Better (sum of mildly, moderately, or much better), No Change, or Worse (sum of mildly, moderately, or much worse).

Time frame: Last Visit (approximately 2 years)

Population: Of the 621 subjects in the Safety Set (SS), 551 are included in this analysis.~Data was not available for 70 subjects at the time of this measurement.

Arm	Measure	Group	Value (NUMBER)
Lacosamide	Patient's Global Impression of Change (PGIC) at Last Visit.	Better	82.6 percentage of participants
Lacosamide	Patient's Global Impression of Change (PGIC) at Last Visit.	No Change	11.4 percentage of participants
Lacosamide	Patient's Global Impression of Change (PGIC) at Last Visit.	Worse	6.0 percentage of participants

Secondary