An Open-Label Long-Term Study Of Pregabalin For The Treatment Of Central Neuropathic Pain

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of the long-term use of pregabalin at doses up to 600 mg/day in patients with central neuropathic pain (post spinal cord injury pain, post stroke pain, and multiple sclerosis pain).

Official Title
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An Open-Label Long-Term Study Of Pregabalin For The Treatment Of Central Neuropathic Pain (Post Spinal Cord Injury Pain, Post Stroke Pain, And Multiple Sclerosis Pain)

Conditions
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Spinal Cord Diseases, Spinal Cord Injuries, Neuralgia, Pain

Intervention / Treatment
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* Drug: pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for subjects to be shifted from Study A0081107 Subjects who completed the 18-week study period in Study A0081107 conducted for chronic neuropathic pain after spinal cord injury; Subjects who completed assessments of all efficacy endpoints until the end of the treatment phase of the preceding Study A0081107 (V7); Inclusion criteria for subjects to be new participants in this study Subjects with central neuropathic pain after stroke or multiple sclerosis; At least 6 months have passed after the onset of central neuropathic pain; Pain VAS at least 40mm in Visit 1 and Visit 2; Exclusion Criteria: Creatinine clearance < 60 mL/min; Platelet count < 100 × 103/mm3 ; White blood cell (WBC) count < 2500 / mm3; Neutrophil count < 1500/ mm3; Subjects who are expected to require surgery during the trial;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin<br>Flexible dosing in 4 weeks followed by 48 weeks maintenance and one week taper period | Drug: pregabalin<br>* Pregabalin capsules taken twice a daily (150-600mg/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peripheral Edema | Number of participants who had peripheral edema in lower extremities. Edema was categorized as follows: trace, pitting 1 (lower leg), 2 (lower leg to knee), and 3 (above knee and /or presacral edema). | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Facial/Periorbital Edema | Number of participants who had facial or periorbital edema. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Generalized or Abdominal Edema | Number of participants who had generalized or abdominal edema. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Localized Pain Related to Deep Vein Thrombosis (DVT) | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling, pitting edema, collateral superficial veins (non-varicose), and skin redness. The symptom was assessed as mild, moderate or severe. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Localized Tenderness Related to Deep Vein Thrombosis (DVT) | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling, pitting edema, collateral superficial veins (non-varicose), and skin redness. The symptom was assessed as mild, moderate or severe. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Swelling Related to Deep Vein Thrombosis (DVT) | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling, pitting edema, collateral superficial veins (non-varicose), and skin redness. The symptom was assessed as mild, moderate or severe. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Pitting Edema Related to Deep Vein Thrombosis (DVT) | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling, pitting edema, collateral superficial veins (non-varicose), and skin redness. The symptom was assessed as mild, moderate or severe. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Collateral Superficial Veins (Non-varicose) Related to Deep Vein Thrombosis (DVT) | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling, pitting edema, collateral superficial veins (non-varicose), and skin redness. The symptom was assessed as mild, moderate or severe. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Skin Redness Related to Deep Vein Thrombosis (DVT) | DVT was defined if a segment of the deep vein of the lower limb was not compressible or a previous compressive vein became non compressive or there was no flow in the underlying vessel. Symptoms of DVT included pain in the lower limb, localized tenderness, swelling, pitting edema, collateral superficial veins (non-varicose), and skin redness. The symptom was assessed as mild, moderate or severe. | Baseline, Weeks 4, 20, 36, 52, and 53 | 
| Number of Participants With Visual Field Deteriorated | Number of participants who had normal visual field at baseline and showed abnormal result after the study treatment, assessed by confrontational visual field test (neurological examination). | 53 weeks | 
| Number of Participants With Deterioration in Neurological Examination Findings | Worsening of the condition relative to baseline was reported as deteriorated. Assessment categories are as follows: normal or abnormal for Cranial Nerve Function, Mental State, and Coordination; normal, mild, moderate, or severe ataxia for Gait; none/absent, normal, or hyper-reflexic for Deep Tendon Reflexes; absent or present for Abnormal Reflexes; normal, mild, moderate, or severe weakness for Muscle Strength; slight, more marked, or considerable increase, or affected parts rigid in flexion or extension for Muscle Tone; absent or present for Sensory Function. | 53 weeks | 
| Number of Participants With Suicidal Ideation According to Sheehan Suicidality Tracking Scale (Sheehan-STS) | The Sheehan-STS is an 8-item prospective rating scale that tracks treatment-emergent suicidal ideation and behaviors. Participants who reported a score of ≥1 (5-point scale ranging from 0: not at all to 4: extremely) for Item 2, 3, 4 or 5 of the Sheehan-STS prognostic scale is considered to have suicidal ideation as the scores are mapped to Category 4 (suicide ideation) of the Columbia Classification Algorithm of Suicide Assessment. | Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) at Each Time Point: Total Scores | The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Range: 0 to 45 for total score. Change = observation mean minus baseline mean. Negative change indicated improvement. | Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 | 
| Change From Baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) at Each Time Point: Sensory Scores | The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Range: 0 to 33 for sensory score. Change = observation mean minus baseline mean. Negative change indicated improvement. | Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 | 
| Change From Baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) at Each Time Point: Affective Scores | The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Range: 0 to 12 for affective score. Change = observation mean minus baseline mean. Negative change indicated improvement. | Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 | 
| Change From Baseline in the Modified Brief Pain Inventory (10 Item) (mBPI-10)Total Scores at Last Evaluation Score | The mBPI-10 is a self administered questionnaire that assesses pain interference with functional activities over the past week. These items are measured on an 11 point scale, ranging from does not interfere (0) to completely interferes (10). A composite score, the Pain Interference Index, will be calculated by averaging the 10 items that comprise the scale. Change = observation mean at Week 52 minus baseline mean. | Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Nervous System Diseases, Therapeutic Uses, Wounds and Injuries, Trauma, Nervous System, pregabalin