Evaluation of the Efficacy and Safety of Entelon Tab. 150mg in Patients With Osteoarthritis of Knee

For 12 Weeks, the Multi-center, Randomized, Double-blinded, Clinical Study to Evaluate the Efficacy and Safety of Entelon Tab. 150mg Compared With Celebrex Capsule in Patients With Osteoarthritis of Knee (Phase III)

This clinical trial is planned to prove Entelon tab. arm is not inferior to Celebrex cap. arm in terms of the efficacy and safety through the change of K-WOMAC's total score sum in patients with osteoarthritis of knee.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Enteron tab. 150mg(vitis vinifera extract 150mg) : twice daily for 12 weeks; Drug: Celebrex cap. (celecoxib 200mg) : once daily, for 12 weeks; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Kyoung-gi Do
    • Bucheon, Kyoung-gi Do, Korea, Republic of, 420-717
      • The Catholic University of Korea, Bucheon St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. both gender,35 years ≤ age ≤ 75 years

2. patients with a diagnosis of OA(osteoarthritis) of the knee within 3 months prior to study participation, as determined by the American College of Rheumatology clinical and radiographic criteria as follows.

   1. knee arthralgia

   2. more than one case among

      • 50 years or over

        • morning stiffness less than 30 min

          • friction sound
   3. osteophyte in radiography
3. Kellgren and Lawrence Scale Grade II~III
4. total sum of K-WOMAC Scale more than 30
5. negative results in pregnancy test of urine in screening period
6. if women in childbearing age, medically reliable contraception or menopause
7. patients who give written consent of agreement to voluntarily participate in the clinical study
8. patients who can read and understand written instructions

Exclusion Criteria:

1. patients whose total sum of K-WOMAC in visit 2 is less than that in visit 1
2. fibromyalgic, anserine bursitis, infectious arthritis, rheumatoid arthritis, ankylosing spondylitis, gout or pseudogout
3. knee OA with secondary causes including major dysplastic or congenital malformation, ochronosis, acromegaly, Hemochromatosis, Wilson's disease or primary osteochondromatosis
4. anatomical malformation, disease of vertebra or other lower extremities or other disease of orthopedics which can disturb the evaluation of the target joint
5. wound, inflammation or avascular necrosis of the target joint or arthroscopy within 6 months prior to study participation
6. patients with administration of injectable hyaluronic acid to the target joint within 6 months prior to study participation
7. severe ischaemic heart diseases, peripheral artery disease and/or cerebrovascular disease, congestive heart failure, active bronchial asthma
8. medical history of malignant tumor
9. active peptic ulcer, gastrointestinal tract bleeding or inflammatory bowel disease
10. hypersensitivity with aspirin, celecoxib, corticosteroid, acetaminophen, sulfonamide derivatives or vitis vinifera or intolerance with fructose, glucose or galactose
11. continuously(1 week or more) oral or intraarticular administration of corticosteroids within 12 weeks prior to study participation
12. pregnant or lactating women
13. patients who have experience to participate in other clinical trial within 4 weeks prior to study participation
14. ALT, AST and Serum Creatinine ≥ 2×UNL
15. drug administration after diagnosing as alcoholic or psychical disease
16. patients whom the investigators judge as improper to participate in this clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex; evening : 1 tab. of placebo Entelon 150mg
Experimental: Entelon tab. 150mg	Drug: Enteron tab. 150mg(vitis vinifera extract 150mg) : twice daily for 12 weeks; morning : 1 tab. of active Entelon 150mg plus 1 cap. of placebo Celebrex; evening : 1 tab. of active Entelon 150mg
Active Comparator: Celebrex cap.	Drug: Celebrex cap. (celecoxib 200mg) : once daily, for 12 weeks; morning : 1 tab. of placebo Entelon 150mg + 1 cap. of active Celebrex; evening : 1 tab. of placebo Entelon 150mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index)	Range of total K-WOMAC score: 0-96 K-WOMAC consists of evaluations of pain, stiffness, physical function. The total K-WOMAC score is the sum of all subscale scores. Higher scores mean a worse outcome. Range of Subscale K-WOMAC score: pain(0-20), stiffness(0-8), physical function(0~68) Higher scores mean a worse outcome. If there is missing data, LOCF(Last Observation Carried Forward) was applied and analyzed.	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Change of Numeric Rating Scale	Numeric Rating Scale is 10 point scale(0~10 score). 0 score: no pain, 10 score: worst possible pain If there is missing data, LOCF(Last Observation Carried Forward) was applied and analyzed.	baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Hanlim Pharm. Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2012
• Primary Completion (Actual): October 15, 2014
• Study Completion (Actual): May 13, 2015

Study Registration Dates

• First Submitted: January 14, 2013
• First Submitted That Met QC Criteria: January 14, 2013
• First Posted (Estimate): January 15, 2013

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 23, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: HL_ENTR_302