Clinical Trial of YYC301 P3 for Treatment of Osteoarthritis of the Knee

Inclusion Criteria:

• Men/Women aged over 20
• Subjects who are diagnosed with one- or both-sided knee osteoarthritis according tothe standards of clinical diagnosis from American College of Rheumatology(ACR)haveknee osteoarthritis pain and meet over three of the following conditions.

1. Older than 50
2. Morning stiffness for less than 30 minutes
3. Crepitus on active motion
4. Bony tenderness
5. Bony enlargement
6. Not have heat-generating site

• Subjects who are diagnosed with degenerative osteoarthritis and have its pain at leastfor over 3 months before the screening visit.
• Subjects who are uncontrolled with pain after administration of Celecoxib at least forover 2 weeks before the randomization and have more than 50mm out of 100mm VAS atrandomization.
• Subjects who voluntarily agree to participate in this clinical trial in writing.

Exclusion Criteria:

• Subjects with rheumatoid arthritis or inflammatory, infectiousand metabolic arthritis.
• Subjects with ochronosis, hemochromatosis, secondary knee osteoarthritis by systemicdisease.
• Subjects who have severe pain such as Sudek's atrophy, Paget's disease and spinal discherniation.
• Subjects with poly-articular affected by severe pain of knee osteoarthritis.
• Subjects who take psychtrophic medicine and narcotic analgesics for over 3 months thatmight affect on pain sensory system.
• Subjects who had Tramadol but there was no improvement in pain.
• Subjects who got the follwing treatment and medicine before the screening;

1. Subjects who had surgery on knee ligaments within a year, cartilage transplantand scarf osteotomy.
2. Subjects who had arthroscopy within 6 months.
3. Subjects with intra-articular knee joint steroid injection within 3 months.
4. Subjects with HA injection in knee joint within 6 months.
5. Subjects with systemic steroid injection within a month(but inhaled steroids)
6. Subjects with knee replacement surgery.

• Subjects who hot the following treatment and medicine before the randomization;

1. Subjects who had Celecoxib, acetaminophen or steroidal/non-steroidalanti-inflammatory drugs except low dose aspirin(before 300mg/day) But,acetaminophen and low dose aspirin (before 300mg/day) are prohibited within 24hours)
2. Nutritional supplements, physical therapy and Korean herbal medicine for kneeosteoarthritis and it pain within 2 weeks.

• Subjects who have to take anticoagulant drugs such as warfarin and coumarin duringthis clinical trial.
• Subjects who took MAO inhibitors within 14 days before the screening or needed to takethese drugs during this clinical trials.
• Subjects with drug and opioid hypersensitivity and who have history.
• Subjects with sulfanilamide allergy and who have history.
• Subjects with asthmma, acute rhinitis, nasal polyp, angioedema, urticaria, allergicreaction to aspirin or any oher NSAIDs(incluing COX-2 inhibitors)
• Subjects with significant investigations - Hyperkalemia(Exceeded 5.5mmol/L)
• Subjects with severe liver dysfunction (ALT or AST of more than 3.0 times the upperlimit of ULN and 1.5 tmines the upper limit of ULN)
• Subjects with severe renal impairment (Serum Creatine > 3x ULN).
• Subjects with active peptic ulcer and gastrointestinal bleeding.
• Severe blood disease (Agranulocytosis, aplastic anemia, hemolytic anemia,Thrombocytopenia, etc.).
• Subjects with Crohn's disease or inflammatory bowel disease such as ulcerative clitis.
• Subjects with congestive heart failure(NYHA 2-4)
• Subjects with severe ischaemic heart disease, peripheral artery disease and/orcerebrovascular disease.
• Subjects with genetic problesa such as galactose intolerance), lapp lactase deficiencyor glucose-galactose malabsorption).
• Subjects with acute alcohol intoxification.
• Subjects who are addicted with took central nervous system drugs such as painkillers,sleeping pills, anti-anxiety medications, etc.
• Subjects with severe bronchopulmonary dysplasia.
• Subjects with head injury history of brain structure lesions which may be in danger ofmental confusion.
• Subjects with epilepsy who are treated properly.
• Subjects who use Tramadol to cure for narcotic withdrawal.
• Subjects who took other clinical drugs more than once within 30 days before theclinical trial.
• Subjects suspected to be pregnant who don't agree with the clinical method which ispermitted medically during clinical trial(Method of hormone contraception,IUD(Intrauterine device) or IUS(Intrauterine system)), tubal ligation, bilateral tuballigation(condom, Diaphragm, etc).
• Pregnant woman and breastfeeding woman.
• Subjects who can increase risk due to clinical test and administraion of drugs or havesevere grade / chronic medical, mental condition or abnormal laboratory result thatmay interfere with the analysis of thest results.
• Any other ineligible condition at the direction of investigator that would beineligible to participate the study.