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

• Sponsor: Hanlim Pharm. Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01768520
• Collaborator: (none)
• Enrollment: 338
• Location: 1
• Arms: 3
• Actual Duration (Months): 34.3
• Patients Per Site Per Month: 9.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	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	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 338 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Jul 2, 2012
• Actual Primary Completion Date: Oct 15, 2014
• Actual Study Completion Date: May 13, 2015

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Placebo	Drug: Placebo; morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex evening : 1 tab. of placebo Entelon 150mg

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

3. knee arthralgia

4. more than one case among

• 50 years or over

• morning stiffness less than 30 min

• friction sound

1. osteophyte in radiography

2. Kellgren and Lawrence Scale Grade II~III

3. total sum of K-WOMAC Scale more than 30

4. negative results in pregnancy test of urine in screening period

5. if women in childbearing age, medically reliable contraception or menopause

6. patients who give written consent of agreement to voluntarily participate in the clinical study

7. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Catholic University of Korea, Bucheon St. Mary's Hospital	Bucheon	Kyoung-gi Do	Korea, Republic of	420-717

Sponsors and Collaborators

• Hanlim Pharm. Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hanlim Pharm. Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01768520
• Other Study ID Numbers: HL_ENTR_302
• First Posted: Jan 15, 2013
• Last Update Posted: Jul 2, 2019
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Celecoxib

Study Results

Participant Flow

Arm/Group Title	Entelon Tab. 150mg	Celebrex Cap.	Placebo
Arm/Group Description	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	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	Placebo: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg
Period Title: Overall Study
STARTED	152	147	39
COMPLETED	120	121	30
NOT COMPLETED	32	26	9

Baseline Characteristics

Arm/Group Title	Entelon Tab. 150mg	Celebrex Cap.	Placebo	Total
Arm/Group Description	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	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	Placebo: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg	Total of all reporting groups
Overall Participants	152	147	39	338
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.41 (7.41)	62.24 (7.12)	64.13 (6.76)	62.09 (7.24)
Sex: Female, Male (Count of Participants)
Female	124 81.6%	105 71.4%	31 79.5%	260 76.9%
Male	28 18.4%	42 28.6%	8 20.5%	78 23.1%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
South Korea	152 100%	147 100%	39 100%	338 100%
Part of Osteoarthritis diagnosis (participants) [Number]
Right knee	72 47.4%	70 47.6%	17 43.6%	159 47%
Left knee	80 52.6%	77 52.4%	22 56.4%	179 53%

Outcome Measures

1. Primary Outcome

Title	the Change of Total Sum of K-WOMAC(Korean The Western Ontario and McMaster Universities Arthritis Index)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Entelon Tab. 150mg	Celebrex Cap.	Placebo
Arm/Group Description	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	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	Placebo: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg
Measure Participants	120	121	30
baseline	51.64 (13.62)	54.57 (14.06)	49.94 (11.81)
12 weeks	30.68 (18.69)	33.88 (20.44)	33.80 (15.98)
change(12 weeks-baseline)	-19.38 (19.79)	-19.26 (18.22)	-16.70 (20.10)

2. Secondary Outcome

Title	the Change of Numeric Rating Scale
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Entelon Tab. 150mg	Celebrex Cap.	Placebo
Arm/Group Description	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	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	Placebo: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg
Measure Participants	120	121	30
baseline	5.62 (1.40)	5.54 (1.73)	5.44 (1.67)
12 weeks	3.57 (2.07)	4.09 (2.09)	4.23 (2.22)
change(12weeks-baseline)	-2.14 (1.81)	-1.54 (2.34)	-1.50 (1.86)

Adverse Events

Time Frame	12Weeks
Arm/Group Title	Entelon Tab. 150mg		Celebrex Cap.		Placebo
Arm/Group Description	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		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		Placebo: 1. morning : 1 tab. of placebo Entelon 150mg + 1 cap. of placebo Celebrex 2. evening : 1 tab. of placebo Entelon 150mg
All Cause Mortality
	Entelon Tab. 150mg		Celebrex Cap.		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/152 (0%)		0/147 (0%)		0/39 (0%)
Serious Adverse Events
	Entelon Tab. 150mg		Celebrex Cap.		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/152 (2%)		4/147 (2.7%)		1/39 (2.6%)
Cardiac disorders
Acute myocardial infarction	0/152 (0%)	0	0/147 (0%)	0	1/39 (2.6%)	1
Eye disorders
Nasolacrimal duct obstruction,Right	1/152 (0.7%)	1	0/147 (0%)	0	0/39 (0%)	0
Gastrointestinal disorders
Epigastric pain	1/152 (0.7%)	1	0/147 (0%)	0	0/39 (0%)	0
Hemorrhoids	0/152 (0%)	0	1/147 (0.7%)	1	0/39 (0%)	0
Infections and infestations
three abscess cavities scattered in both hepatic lobes	0/152 (0%)	0	1/147 (0.7%)	1	0/39 (0%)	0
Injury, poisoning and procedural complications
Multiple fractures	1/152 (0.7%)	1	0/147 (0%)	0	0/39 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Esophageal cancer	0/152 (0%)	0	1/147 (0.7%)	1	0/39 (0%)	0
Nervous system disorders
Middle cerebral artery stenosis	0/152 (0%)	0	1/147 (0.7%)	1	0/39 (0%)	0
Other (Not Including Serious) Adverse Events
	Entelon Tab. 150mg		Celebrex Cap.		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/152 (9.2%)		22/147 (15%)		16/39 (41%)
Gastrointestinal disorders
Constipation	0/152 (0%)	0	0/147 (0%)	0	1/39 (2.6%)	1
Abdominal pain upper	6/152 (3.9%)	6	3/147 (2%)	3	2/39 (5.1%)	2
Dyspepsia	1/152 (0.7%)	1	3/147 (2%)	3	0/39 (0%)	0
Gastritis	0/152 (0%)	0	2/147 (1.4%)	2	1/39 (2.6%)	1
Nausea	3/152 (2%)	3	0/147 (0%)	0	1/39 (2.6%)	1
Infections and infestations
Herpes zoster	0/152 (0%)	0	3/147 (2%)	3	0/39 (0%)	0
Nasopharyngitis	1/152 (0.7%)	1	5/147 (3.4%)	5	0/39 (0%)	0
Upper respiratory tract infection	1/152 (0.7%)	1	2/147 (1.4%)	2	2/39 (5.1%)	2
Investigations
Alanine aminotransferase increased	0/152 (0%)	0	0/147 (0%)	0	2/39 (5.1%)	2
Aspartate aminotransferase increased	0/152 (0%)	0	0/147 (0%)	0	3/39 (7.7%)	3
Nervous system disorders
Headache	2/152 (1.3%)	2	2/147 (1.4%)	2	2/39 (5.1%)	2
Renal and urinary disorders
Nocturia	0/152 (0%)	0	0/147 (0%)	0	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/152 (0%)	0	2/147 (1.4%)	2	1/39 (2.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.