Trial Outcomes & Findings for An Open-label Continuation Trial to Assess the Continued Efficacy and Safety of Ascending Doses of Lacosamide in Subjects With Chronic Refractory Neuropathic Pain (NCT NCT00237458)

NCT ID: NCT00237458

Last Updated: 2017-08-28

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 7 participants
• Primary outcome timeframe: From Baseline Visit to Final Week of Treatment (approximately 10 years)
• Results posted on: 2017-08-28

Participant Flow

The study started in May 2001 with subjects from Germany. The primary completion date and study completion date occurred in March 2011.

One subject was discontinued on the study due to the Adverse Event of Vertigo. However, the Termination page of the Case Report Form reflected that the subject withdrew consent. Therefore, the Participant Flow will reflect 3 subjects did not complete the study, while the subjects withdrawing from Adverse Events will reflect 2.

Participant milestones

Measure	Lacosamide Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Overall Study STARTED	7
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Lacosamide Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Overall Study Lack of Efficacy	1
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

An Open-label Continuation Trial to Assess the Continued Efficacy and Safety of Ascending Doses of Lacosamide in Subjects With Chronic Refractory Neuropathic Pain

Baseline characteristics by cohort

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	47.4 years STANDARD_DEVIATION 10.18 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Region of Enrollment Germany	7 participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 10 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Number of Subjects Reporting At Least 1 Treatment-Emergent Adverse Event (TEAE) During The Treatment Period.	7 participants

PRIMARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 10 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Number of Subjects Withdrawing From Study Due To A Treatment-Emergent Adverse Event (TEAE) During The Treatment Period.	2 participants

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

The Average Daily Pain Score is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst pain ever experienced).

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Within-Subject Change In Average Daily Pain Score During the Treatment Period.	-2.9 units on a scale Standard Deviation 3.38

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Each individual cardinal symptom of pain is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst possible pain).

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Within-Subject Change In The Perception Of Each Of The Individual Cardinal Symptoms of Pain During The Treatment Period - Shooting.	-2.3 units on a scale Standard Deviation 4.27

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Each individual cardinal symptom of pain is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst possible pain).

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Within-Subject Change In The Perception Of Each Of The Individual Cardinal Symptoms of Pain During The Treatment Period - Burning.	0.4 units on a scale Standard Deviation 2.15

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Each individual cardinal symptom of pain is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst possible pain).

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Within-Subject Change In The Perception Of Each Of The Individual Cardinal Symptoms of Pain During The Treatment Period - Paraesthesiae.	-2.1 units on a scale Standard Deviation 3.34

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Each individual cardinal symptom of pain is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst possible pain).

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Within-Subject Change In The Perception Of Each Of The Individual Cardinal Symptoms of Pain During The Treatment Period - Numbness.	-2.4 units on a scale Standard Deviation 3.78

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

Each individual cardinal symptom of pain is calculated using an 11-point Likert scale, ranging from 0 (no pain) to 10 (worst possible pain).

Allodynia is defined as neuropathic pain caused by normally innocuous stimuli becoming painful.

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Within-Subject Change In The Perception Of Each Of The Individual Cardinal Symptoms of Pain During The Treatment Period - Allodynia.	0.6 units on a scale Standard Deviation 2.37

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

The Subject's Global Impression of Change is a self-evaluation by the subject of their overall change in relief of neuropathic pain since the beginning of the study rated on a 7-point scale ranging from:

1. Much better

2. Moderately better

3. Mildly better

4. No change

5. Mildly worse

6. Moderately worse

7. Much worse

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Subject's Global Impression of Change In Pain During The Treatment Period. Better	85.7 percentage of participants
Subject's Global Impression of Change In Pain During The Treatment Period. No Change	14.3 percentage of participants
Subject's Global Impression of Change In Pain During The Treatment Period. Worse	0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline Visit to Final Week of Treatment (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 7 are included in this analysis.

The Investigator's Global Impression of Change is a physician's assessment of the patient's overall change in relief of neuropathic pain since the beginning of the study rated on a 7-point scale ranging from:

1. Much better

2. Moderately better

3. Mildly better

4. No change

5. Mildly worse

6. Moderately worse

7. Much worse

Outcome measures

Measure	Lacosamide n=7 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Investigator's Global Impression of Change In Pain During The Treatment Period. Better	85.7 percentage of participants
Investigator's Global Impression of Change In Pain During The Treatment Period. No Change	14.3 percentage of participants
Investigator's Global Impression of Change In Pain During The Treatment Period. Worse	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline Period (approximately 1 week)

Population: Of the 7 subjects in the Safety Set (SS), 4 are included in this analysis.

The percentage of days where rescue medication was taken is summarized by visit and by Treatment Phase (Baseline, Titration, and Titration + Treatment).

The percentage of days of rescue medication use is defined as the number of days observed within the visit/study phase with rescue medication divided by the number of days in the visit/study phase times 100 for subjects who had taken the rescue medication.

Summary statistics include mean and standard deviation.

Outcome measures

Measure	Lacosamide n=4 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Percentage of Days With Concomitant Pain ("Rescue") Medications Taken During Baseline Phase.	100 percentage of days Standard Deviation 0.00

SECONDARY outcome

Timeframe: Titration Period (approximately 6 weeks)

Population: Of the 7 subjects in the Safety Set (SS), 4 are included in this analysis.

The percentage of days where rescue medication was taken is summarized by visit and by Treatment Phase (Baseline, Titration, and Titration + Treatment).

The percentage of days of rescue medication use is defined as the number of days observed within the visit/study phase with rescue medication divided by the number of days in the visit/study phase times 100 for subjects who had taken the rescue medication.

Summary statistics include mean and standard deviation.

Outcome measures

Measure	Lacosamide n=4 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Percentage of Days With Concomitant Pain ("Rescue") Medications Taken During Titration Phase.	51.3 percentage of days Standard Deviation 36.98

SECONDARY outcome

Timeframe: From Titration Phase through Treatment Phase (approximately 9 years)

Population: Of the 7 subjects in the Safety Set (SS), 5 are included in this analysis.

The percentage of days where rescue medication was taken is summarized by visit and by Treatment Phase (Baseline, Titration, and Titration + Treatment).

The percentage of days of rescue medication use is defined as the number of days observed within the visit/study phase with rescue medication divided by the number of days in the visit/study phase times 100 for subjects who had taken the rescue medication.

Summary statistics include mean and standard deviation.

Outcome measures

Measure	Lacosamide n=5 Participants Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Percentage of Days With Concomitant Pain ("Rescue") Medications Taken During Titration and Treatment Phases.	12.3 percentage of days Standard Deviation 7.91

Adverse Events

Lacosamide

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lacosamide n=7 participants at risk Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
General disorders Chest Pain	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
General disorders Pain	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Injury, poisoning and procedural complications Femur Fracture	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Weight Decreased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Nervous system disorders Syncope	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Vascular disorders Circulatory Collapse	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.

Other adverse events

Measure	Lacosamide n=7 participants at risk Dosage: Lacosamide up to 400 mg/day; Dosage form: Film-coated tablets; Dosage Frequency and Duration: Two times per day; 9.5 years
Cardiac disorders Sinus Bradycardia	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Cardiac disorders Sinus Tachycardia	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Ear and labyrinth disorders Vertigo	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Eye disorders Conjunctival Haemorrhage	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Eye disorders Iritis	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Gastrointestinal disorders Diarrhoea	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Gastrointestinal disorders Enterocolitis Haemorrhagic	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Gastrointestinal disorders Peptic Ulcer	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Gastrointestinal disorders Stomach discomfort	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
General disorders Asthenia	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
General disorders Fatigue	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Gastroenteritis	14.3% 1/7 • Number of events 3 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Influenza	28.6% 2/7 • Number of events 3 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Localised Infection	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Lower Respiratory Tract Infection	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Mumps	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Nasopharyngitis	14.3% 1/7 • Number of events 5 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Pharyngitis	28.6% 2/7 • Number of events 4 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Sinusitis	14.3% 1/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Upper Respiratory Tract Infection	42.9% 3/7 • Number of events 14 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Infections and infestations Viral Infection	28.6% 2/7 • Number of events 3 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Injury, poisoning and procedural complications Foot Fracture	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Injury, poisoning and procedural complications Fractured Coccyx	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Injury, poisoning and procedural complications Joint Sprain	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Injury, poisoning and procedural complications Muscle Strain	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Alanine Aminotransferase Increased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Aspartate Aminotransferase Increased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Basophil Count Increased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Blood Phosphorus Increased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Blood Sodium Decreased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Electrocardiogram QT Corrected Interval Prolonged	14.3% 1/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Electrocardiogram QT Prolonged	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Gamma-glutamyltransferase Increased	14.3% 1/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Neutrophil Count Decreased	42.9% 3/7 • Number of events 4 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Platelet Count Decreased	28.6% 2/7 • Number of events 4 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Investigations Thyroxine Free Increased	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Metabolism and nutrition disorders Diabetes Mellitus	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Metabolism and nutrition disorders Diabetes Mellitus Non-insulin-dependent	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Metabolism and nutrition disorders Hypercholesterolaemia	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Musculoskeletal and connective tissue disorders Groin Pain	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Musculoskeletal and connective tissue disorders Muscle Spasms	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Musculoskeletal and connective tissue disorders Neck Pain	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Musculoskeletal and connective tissue disorders Pain In Extremity	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Nervous system disorders Dizziness	57.1% 4/7 • Number of events 5 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Nervous system disorders Headache	28.6% 2/7 • Number of events 9 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Nervous system disorders Tension Headache	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Psychiatric disorders Depression	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Psychiatric disorders Sleep disorder	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Reproductive system and breast disorders Menorrhagia	14.3% 1/7 • Number of events 3 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Skin and subcutaneous tissue disorders Hyperhidrosis	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Number of events 1 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Skin and subcutaneous tissue disorders Rash	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.
Vascular disorders Hypertension	28.6% 2/7 • Number of events 2 • The Time Frame for Adverse Event Reporting was the maximum exposure time of 9.5 years.

Additional Information

UCB (Study Director)

UCB Clinical Trial Call Center

Phone: +1 887 822 9493

Results disclosure agreements

• Principal investigator is a sponsor employee UCB has \> 60 but \<= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that the results shall be published regardless of outcome.
• Publication restrictions are in place

Restriction type: OTHER