Knee Osteoarthritis
Conditions
Brief summary
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.
Interventions
DRUGEnteron tab. 150mg(vitis vinifera extract 150mg) : twice daily for 12 weeks
1. morning : 1 tab. of active Entelon 150mg plus 1 cap. of placebo Celebrex 2. evening : 1 tab. of active Entelon 150mg
DRUGCelebrex cap. (celecoxib 200mg) : once daily, for 12 weeks
1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of active Celebrex 2. evening : 1 tab. of placebo Entelon 150mg
DRUGPlacebo
1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg
Sponsors
Hanlim Pharm. Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | baseline and 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Change of Numeric Rating Scale | baseline and 12 weeks | 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. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entelon Tab. 150mg Enteron tab. 150mg(vitis vinifera extract 150mg) : twice daily for 12 weeks: 1. morning : 1 tab. of active Entelon 150mg plus 1 cap. of placebo Celebrex 2. evening : 1 tab. of active Entelon 150mg | 152 |
| Celebrex Cap. Celebrex cap. (celecoxib 200mg) : once daily, for 12 weeks: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of active Celebrex 2. evening : 1 tab. of placebo Entelon 150mg | 147 |
| Placebo Placebo: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg | 39 |
| Total | 338 |
Baseline characteristics
| Characteristic | Entelon Tab. 150mg | Celebrex Cap. | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 61.41 years STANDARD_DEVIATION 7.41 | 62.24 years STANDARD_DEVIATION 7.12 | 64.13 years STANDARD_DEVIATION 6.76 | 62.09 years STANDARD_DEVIATION 7.24 |
| Part of Osteoarthritis diagnosis Left knee | 80 participants | 77 participants | 22 participants | 179 participants |
| Part of Osteoarthritis diagnosis Right knee | 72 participants | 70 participants | 17 participants | 159 participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment South Korea | 152 participants | 147 participants | 39 participants | 338 participants |
| Sex: Female, Male Female | 124 Participants | 105 Participants | 31 Participants | 260 Participants |
| Sex: Female, Male Male | 28 Participants | 42 Participants | 8 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 152 | 0 / 147 | 0 / 39 |
| other Total, other adverse events | 14 / 152 | 22 / 147 | 16 / 39 |
| serious Total, serious adverse events | 3 / 152 | 4 / 147 | 1 / 39 |
Outcome results
Primary
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.
Time frame: baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entelon Tab. 150mg | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | 12 weeks | 30.68 score on a scale | Standard Deviation 18.69 |
| Entelon Tab. 150mg | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | baseline | 51.64 score on a scale | Standard Deviation 13.62 |
| Entelon Tab. 150mg | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | change(12 weeks-baseline) | -19.38 score on a scale | Standard Deviation 19.79 |
| Celebrex Cap. | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | baseline | 54.57 score on a scale | Standard Deviation 14.06 |
| Celebrex Cap. | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | change(12 weeks-baseline) | -19.26 score on a scale | Standard Deviation 18.22 |
| Celebrex Cap. | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | 12 weeks | 33.88 score on a scale | Standard Deviation 20.44 |
| Placebo | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | change(12 weeks-baseline) | -16.70 score on a scale | Standard Deviation 20.1 |
| Placebo | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | 12 weeks | 33.80 score on a scale | Standard Deviation 15.98 |
| Placebo | the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index) | baseline | 49.94 score on a scale | Standard Deviation 11.81 |
Secondary
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.
Time frame: baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Entelon Tab. 150mg | the Change of Numeric Rating Scale | change(12weeks-baseline) | -2.14 score on a scale | Standard Deviation 1.81 |
| Entelon Tab. 150mg | the Change of Numeric Rating Scale | 12 weeks | 3.57 score on a scale | Standard Deviation 2.07 |
| Entelon Tab. 150mg | the Change of Numeric Rating Scale | baseline | 5.62 score on a scale | Standard Deviation 1.4 |
| Celebrex Cap. | the Change of Numeric Rating Scale | change(12weeks-baseline) | -1.54 score on a scale | Standard Deviation 2.34 |
| Celebrex Cap. | the Change of Numeric Rating Scale | baseline | 5.54 score on a scale | Standard Deviation 1.73 |
| Celebrex Cap. | the Change of Numeric Rating Scale | 12 weeks | 4.09 score on a scale | Standard Deviation 2.09 |
| Placebo | the Change of Numeric Rating Scale | change(12weeks-baseline) | -1.50 score on a scale | Standard Deviation 1.86 |
| Placebo | the Change of Numeric Rating Scale | 12 weeks | 4.23 score on a scale | Standard Deviation 2.22 |
| Placebo | the Change of Numeric Rating Scale | baseline | 5.44 score on a scale | Standard Deviation 1.67 |