A Study to Evaluate Efficacy of 『Opast Tablet』for Neurologic Claudication in Patients With Lumbar Spinal Stenosis

Study Overview
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Brief Summary
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This trial is a comparative study of Opast tablet and Rikalin capsule 75mg and Rikalin capsule 75mg in combination with Opast tablet to evaluate improvement effectiveness of Opast tablet on subjective symptoms and neurologic claudication in patients with lumbar spinal stenosis.

Detailed Description
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Subjects who provided written consents voluntarily after receiving a sufficient explanation about this trial will be assigned to one of groups(study group; limaprost, comparative group 1; pregabalin, comparative group 2; limaprost+ pregabalin) by randomization at the rate of 1:1:1. Subjects will take assigned investigational drugs thrice a day for eight weeks by double-blind and double-dummy methods, and they will visit the site two times at intervals of four weeks. At each site visit point, the improvement effectiveness will be comparatively evaluated by evaluation of following endpoints; Efficacy endpoints: ICD(initial claudication distance) at treadmill test (speed:3km/hr, grade:0%), VAS in pain on lower extremities, EQ-5D and ODI Safety endpoints: Vital signs, hematology/blood chemistry tests and adverse events, etc.

Official Title
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A Randomized, Double-Blind, Comparative, Multi-Center, Phase Ⅳ Clinical Trial to Evaluate Efficacy of 『Opast Tablet』for Neurologic Claudication in Patients With Lumbar Spinal Stenosis

Conditions
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Neurologic Claudication in Patients With Lumbar Spinal Stenosis

Intervention / Treatment
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* Drug: Limaprost
* Drug: Pregabalin
* Drug: Placebo(for Pregabalin)
* Drug: Placebo(for Limaprost)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is fully understand the clinical trial and obtained informed consent. Age 20-75years. Patients with a confirmed diagnosis of waist of spinal canal stenosis. Limb pain caused by waist of spinal canal stenosis index of VAS 3 or more patients. Subject who has numbness symptom on lower extremity(ies) and intermittent claudication that are due to spinal canal stenosis and fulfills both of following criteria at the same time When screening visit, a medical examination by interview had the following symptoms in subjects ; In daily life walking, when walked by within 20 minutes on flatland, the subject can feel the symptoms (numbness, pain or tightness on lower extremity(ies), etc.) Subject who experienced numbness, pain, tightness or other similar symptom(s) on lower extremity within 15 minutes from test start at baseline(D1) evaluation. speed: 3km/hr, grade:0%, posture: should keep their lumbar spinal extended Exclusion Criteria: Pregnant or lactating women of childbearing potential not employing adequate contraception. Patients who have the hereditary problem of galactose intolerance, Lapp lactase deficiency or grape sugar-galactose absorption defect. Patients with systemic disease affecting the lower limbs. Patients who have cauda equina syndrome. Patients with acute osteoporosis compression fracture in lumbar vertebra. Patients who have gait disturbance of degenerative arthritis by hip joint, knee joint, ankle joint. At least one month before the start of the study, patients use of steroid drug except lumbar dura mater. 6 month before the start of the study, patients with ischaemic disease in blood vessel, lung or the coronary artery, varicose artery. Patients with lumbar necrosis in head of femur avascular necrosis, necrotic foot ulcer. Patients surgery by lumbar fusion and lumbar decompression. Patients with renal disease or need to hemodialysis. serum creatinine > 2xUNL 3 month before the start of the study, patients participated in another clinical research. Patients with difficult understanding spirit incompetence, lack of will or language barrier. The investigator judged seriously ill patients need surgery patient.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Limaprost & Placebo<br>Limaprost 5㎍ tablet and a capsule of Pegabalin-Placebo thrice a day for 8 weeks. | Drug: Limaprost<br> <br> * Other names: Opast tablet;Drug: Placebo(for Pregabalin)<br>* mimic Pregabalin 75mg capsule<br>|
| Active Comparator: Pregabalin & Placebo<br>Pregabalin 75mg capsule and a tablet of Limaprost-Placebo thrice a day for 8 weeks. | Drug: Pregabalin<br> <br> * Other names: Rikalin capsule 75mg;Drug: Placebo(for Limaprost)<br>* mimic Limaprost tablet<br>|
| Active Comparator: Limaprost+Pregabalin<br>Limaprost 5㎍ tablet and Pregabalin 75mg capsule thrice a day for 8 weeks. | Drug: Limaprost<br> <br> * Other names: Opast tablet;Drug: Pregabalin<br> <br> * Other names: Rikalin capsule 75mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline-adjusted Oswestry Disability Index score at 8 weeks after treatment | baseline-adjusted Oswestry Disability Index score at 8 weeks after treatment between study group(limaprost) and comparative group1(pregabalin) and combination group (limaprost + pregabalin) | up to 8 weeks after first administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial Claudication Distance(ICD) on treadmill test | Improvement of ICD at 4 weeks after first administration compared to baseline, between study group(limaprost) and comparative group1(pregabalin) Improvement of ICD at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group 2(limaprost+ pregabalin) | 4 and 8 weeks after first administration | 
| lower extremity pain score measured by Visual Analog Scale(VAS) 10cm | Change in VAS at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group1(pregabalin) Change in VAS at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group 2(limaprost+ pregabalin) | 4 and 8 weeks after first administration | 
| Mean ratio of change in score of EuroQuol 5D (EQ-5D) | Change in EQ-5D at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group1(pregabalin) Change in EQ-5D at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group 2(limaprost+ pregabalin) | 4 and 8 weeks after first administration | 
| Mean ratio of change in score of Oswestry Disability Index(ODI) | Change in ODI at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group1(pregabalin) Change in ODI at 4, 8 weeks after first administration compared to baseline, between study group(limaprost) and comparative group 2(limaprost+ pregabalin) | 4 and 8 weeks after first administration |