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

• ClinicalTrials.gov Identifier: NCT01202227
• Recruitment Status: Completed
• First Posted: September 15, 2010
• Results First Posted: May 17, 2013
• Last Update Posted: January 28, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Spinal Cord Diseases; Spinal Cord Injuries; Neuralgia; Pain	Drug: pregabalin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: September 2010
• Actual Primary Completion Date: March 2012
• Actual Study Completion Date: March 2012

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Peripheral Edema [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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).
2. Number of Participants With Facial/Periorbital Edema [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   Number of participants who had facial or periorbital edema.
3. Number of Participants With Generalized or Abdominal Edema [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   Number of participants who had generalized or abdominal edema.
4. Number of Participants With Localized Pain Related to Deep Vein Thrombosis (DVT) [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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.
5. Number of Participants With Localized Tenderness Related to Deep Vein Thrombosis (DVT) [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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.
6. Number of Participants With Swelling Related to Deep Vein Thrombosis (DVT) [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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.
7. Number of Participants With Pitting Edema Related to Deep Vein Thrombosis (DVT) [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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.
8. Number of Participants With Collateral Superficial Veins (Non-varicose) Related to Deep Vein Thrombosis (DVT) [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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.
9. Number of Participants With Skin Redness Related to Deep Vein Thrombosis (DVT) [ Time Frame: Baseline, Weeks 4, 20, 36, 52, and 53 ]
   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.
10. Number of Participants With Visual Field Deteriorated [ Time Frame: 53 weeks ]
    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).
11. Number of Participants With Deterioration in Neurological Examination Findings [ Time Frame: 53 weeks ]
    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.
12. Number of Participants With Suicidal Ideation According to Sheehan Suicidality Tracking Scale (Sheehan-STS) [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 ]
    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.

Secondary Outcome Measures :

1. Change From Baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) at Each Time Point: Total Scores [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 ]

   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.

2. Change From Baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) at Each Time Point: Sensory Scores [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 ]

   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.

3. Change From Baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) at Each Time Point: Affective Scores [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 20, 28, 36, 44, and 52 ]

   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.

4. Change From Baseline in the Modified Brief Pain Inventory (10 Item) (mBPI-10)Total Scores at Last Evaluation Score [ Time Frame: Baseline, Week 52 ]

   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.

Eligibility Criteria

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

Criteria

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;

Contacts and Locations

Locations

Japan

Chubu Rosai Hospital

Nagoya, Aichi, Japan

Kimura Clinic

Nagoya, Aichi, Japan

Nagoya Kyoritsu Clinic

Nagoya, Aichi, Japan

Senboku Kumiai General Hospital

Daisen, Akita, Japan

Go neurosurgical clinic

Chikushi-gun, Fukuoka, Japan

Spinal Injuries Center

Iizuka, Fukuoka, Japan

Brain Attack Center Ota Memorial Hospital

Fukuyama, Hiroshima, Japan

Hokkaido Chuo Rosai Hospital Sekison Center

Bibai, Hokkaido, Japan

Hakodate Central General Hospital

Hakodate, Hokkaido, Japan

Kobe Tokushukai Hospital

Kobe, Hyogo, Japan

Aida Kinen Rehabilitation Hospital

Moriya, Ibaraki, Japan

General Hanamaki Hospital

Hanamaki, Iwate, Japan

Uchida Rehabilitation Orthopedic Clinic

Kawasaki, Kanagawa, Japan

Kumamoto Rehabilitation Hospital

Kikuchi-gun, Kumamoto, Japan

Sendai Pain Clinic

Sendai-city, Miyagi, Japan

Kohnan Hospital

Sendai, Miyagi, Japan

National Hospital Organization Niigata National Hospital

Kashiwazaki, Niigata, Japan

Nakamura Hospital

Beppu, Oita, Japan

Kitasato University Kitasato Institute Medical Center Hospital

Kitamoto, Saitama, Japan

Kamitsuga General Hospital

Kanuma, Tochigi, Japan

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

Jukoukai hospital

Koto-ku, Tokyo, Japan

National Hospital Organization, Murayama Medical Center

Musashimurayama-shi, Tokyo, Japan

Okitama Public General Hospital

Higashiokitama-gun, Yamagata, Japan

Tokushima University Hospital

Tokushima, Japan

National Hospital Organization Yamagata Hospital

Yamagata, Japan

Sponsors and Collaborators

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

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01202227
• Other Study ID Numbers: A0081252
• First Posted: September 15, 2010
• Results First Posted: May 17, 2013
• Last Update Posted: January 28, 2021
• Last Verified: April 2013

Keywords provided by Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. ):

Central Nervous System Diseases; Therapeutic Uses; Wounds and Injuries; Trauma; Nervous System; pregabalin

Additional relevant MeSH terms:

Spinal Cord Injuries; Neuralgia; Spinal Cord Diseases; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Peripheral Nervous System Diseases; Neuromuscular Diseases; Pain; Neurologic Manifestations; Pregabalin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs