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

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)

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).

Study Overview

• Status: Completed
• Conditions: Pain; Neuralgia; Spinal Cord Diseases; Spinal Cord Injuries
• Intervention / Treatment: Drug: pregabalin

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokushima, Japan
    • Tokushima University Hospital
  • Yamagata, Japan
    • National Hospital Organization Yamagata Hospital
  • Aichi
    • Nagoya, Aichi, Japan
      • Kimura Clinic
    • Nagoya, Aichi, Japan
      • Chubu Rosai Hospital
    • Nagoya, Aichi, Japan
      • Nagoya Kyoritsu Clinic
  • Akita
    • Daisen, Akita, Japan
      • Senboku Kumiai General Hospital
  • Fukuoka
    • Chikushi-gun, Fukuoka, Japan
      • Go Neurosurgical Clinic
    • Iizuka, Fukuoka, Japan
      • Spinal Injuries Center
  • Hiroshima
    • Fukuyama, Hiroshima, Japan
      • Brain Attack Center Ota Memorial Hospital
  • Hokkaido
    • Bibai, Hokkaido, Japan
      • Hokkaido Chuo Rosai Hospital Sekison Center
    • Hakodate, Hokkaido, Japan
      • Hakodate Central General Hospital
  • Hyogo
    • Kobe, Hyogo, Japan
      • Kobe Tokushukai Hospital
  • Ibaraki
    • Moriya, Ibaraki, Japan
      • Aida Kinen Rehabilitation Hospital
  • Iwate
    • Hanamaki, Iwate, Japan
      • General Hanamaki Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan
      • Uchida Rehabilitation Orthopedic Clinic
  • Kumamoto
    • Kikuchi-gun, Kumamoto, Japan
      • Kumamoto Rehabilitation Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • Kohnan Hospital
    • Sendai-city, Miyagi, Japan
      • Sendai Pain Clinic
  • Niigata
    • Kashiwazaki, Niigata, Japan
      • National Hospital Organization Niigata National Hospital
  • Oita
    • Beppu, Oita, Japan
      • Nakamura Hospital
  • Saitama
    • Kitamoto, Saitama, Japan
      • Kitasato University Kitasato Institute Medical Center Hospital
  • Tochigi
    • Kanuma, Tochigi, Japan
      • Kamitsuga General Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Juntendo University Hospital
    • Koto-ku, Tokyo, Japan
      • Jukoukai hospital
    • Musashimurayama-shi, Tokyo, Japan
      • National Hospital Organization, Murayama Medical Center
  • Yamagata
    • Higashiokitama-gun, Yamagata, Japan
      • Okitama Public General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Onouchi K, Koga H, Yokoyama K, Yoshiyama T. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. J Pain Res. 2014 Jul 28;7:439-47. doi: 10.2147/JPR.S63028. eCollection 2014.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: September 13, 2010
• First Posted (Estimate): September 15, 2010

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: pregabalin; Central Nervous System Diseases; Trauma; Therapeutic Uses; Nervous System; Wounds and Injuries
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Neuralgia; Spinal Cord Diseases; Spinal Cord Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081252