Patient case (clinical description): A 66-year-old woman comes to the office due to joint pain in the hands and periodic morning stiffness that lasts less than 15 minutes.  The pain is moderately severe and worsens with daily activity. The patient used Tylenol with minimal relief.  Past medical history is notable for hypertension and hypercholesteremia.  Physical examination shows firm nodules over the distal interphalangeal joints, bilaterally. The patient has pain in her knees as well. The knees are stiff in the morning for less than 30 minutes and become worse with climbing stairs. She has some sensation of bone friction during activity. X-ray shows narrowing of the joint space, subchondral bone sclerosis and osteophyte formation along the joints.

Patient's own account: I'm a 66-year-old woman and I went to my doctor's office because of a bloody joint pain in my hands that has been lasting for a while. The pain comes and go in the morning usually. I feel like a stiffness that last less than 15 minutes. The pain is moderately severe but it gets worse when I'm using my hands. I used Tylenol which helped a little. Apart from that, I suffer from hypertension and high cholesterol. The doctor made me notice that I have bumps around both of my hand joints. I also suffer from my knees and they are also stiff in the morning for around 30 min. It's even worse when I climb up the stairs! I also feel like my bones are rubbing against each other when I'm moving. The X-ray showed that I have narrow joint space, I have sclerosis, and abnormal growths of bone along my joints.

Clinical trial: A Single Center 2-way Crossover Study to Investigate the Mechanism of Action of Etoricoxib in Subjects With Osteoarthritis Knee Pain

Eligibility criteria:
Inclusion Criteria:

          1. Written informed consent (IRB/IEC specific) has been obtained prior to initiation of
             any protocol required procedures.

          2. Male or female between 40 and 75 years of age. Females of childbearing potential must
             have a negative urine pregnancy test at screening.

          3. Body weight >40 kg and <150 kg with a body mass index (BMI) between 19-40 kg/m2
             inclusive.

          4. Idiopathic osteoarthritic knee pain diagnosed in accordance with the American College
             of Rheumatology modified clinical classification criteria (Altman et al, 1986) and
             verified radiologically as Kellgren-Lawrence grade I, II or III (Kellgren and
             Lawrence, 1957) at the index knee. The clinical diagnosis of OA will be confirmed by
             the ACR clinical and radiographic criteria for classification of idiopathic OA based
             upon the following criteria (index knee):

               1. Knee pain for at least 14 days per month for the 3 months before study entry.

               2. Osteophytes (with radiographic evidence).

               3. And at least 1 of the following 3 conditions: Age >50, or morning stiffness <30
                  minutes, or crepitus.

               4. X-ray images of the knee joints are available confirming OA. X-ray images older
                  than12 months cannot be used. New photos are needed to confirm the diagnostic
                  criteria for OA.

          5. For the index knee, the average of the worst daily pain score over the last 14 days
             prior to day 0 must be 4.0 to 9.0. The 14-day average score will be derived from worst
             daily pain scores recorded in a diary for the index knee.

          6. Discontinued use of all analgesic medications (including over-the-counter analgesics/
             Non-Steroidal Anti-Inflammatory Drug at least 3 days prior to visit 2 (subjects are
             allowed limited use of analgesic medications).

          7. Have agreed to maintain the same activity level throughout the course of the study.

        Exclusion Criteria:

          1. Have a history of recurrent seizures other than febrile seizures.

          2. Have a history of frequent and/or severe allergic reactions with multiple medications.

          3. Have a current or recent history, as determined by the investigator or his delegates,
             of severe, progressive, and/or uncontrolled renal, hepatic, hematological,
             gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric or cerebral
             disease which could interfere with the subject's participation in the study.

          4. At screening, have an abnormality in the 12-lead ECG that, in the opinion of the
             investigator, increases the risks associated with participation in the study. In
             addition, subjects with following findings will be excluded:

               1. Confirmed Bazett's corrected QT (QTcB) interval > 450 msec for men and > 470 msec
                  for women at screening. If QTcB is prolonged a second ECG will be taken to
                  confirm the finding; (additional ECGs may be performed if required),

               2. Bundle branch blocks and other conduction abnormalities other than mild first
                  degree atrio-ventricular block, left anterior hemi block due to left axis
                  deviation and right bundle branch block of benign origin i.e. not caused by other
                  cardiac disease,

               3. Irregular rhythms other than sinus arrhythmia or occasional supraventricular or
                  ventricular ectopic beats,

               4. History of unexplained syncope,

               5. Family history of unexplained sudden death or sudden death due to long QT
                  syndrome,

               6. T-wave configurations are not of sufficient quality for assessing QT interval
                  determination, as assessed by the investigator.

          5. Have an alanine aminotransaminase > 2.5 times Upper Limit of Normal (ULN) at
             screening, based on reference ranges of the local laboratory. Moderate or greater
             hepatic impairment.

          6. Have prior renal transplant, current renal dialysis or severe renal insufficiency
             (determined by a derived glomerular filtration rate using Cockcroft Gault formula of
             ≤30 ml/min/1,73m² calculated by the local lab), or serum creatinine laboratory value
             >1.5 times ULN, based on the reference ranges of the local laboratory.

          7. Have active peptic ulcer or gastrointestinal bleeding.

          8. Have known inflammatory intestinal disease.

          9. Subject with ischemic heart disease, peripheral arterial disease and/or
             cerebrovascular disease.

         10. Subject with congestive heart failure (NYHA II-IV).

         11. Subject with uncontrolled arterial hypertension (>160/90).

         12. Subject with diabetes mellitus and documented atherosclerosis.

         13. History of bronchospasms, acute rhinitis, nasal polyps, angioneurotic edema, urticaria
             or other type of allergic reaction after having used acetylic acid or NSAID, inclusive
             COX-2 inhibitors.

         14. Is allergic to the active ingredient of etoricoxib or one or more of the excipients.

         15. Pregnant female, breast feeding or planning a pregnancy during the study period.
             Females of child-bearing potential, not using a reliable means of contraception.

         16. Subject with an active malignancy of any type or a history of malignancy within the
             last 5 years (except basal cell carcinoma of the skin that has been excised prior to
             study start).

         17. Are taking any excluded medications (analgesic medications) that cannot be
             discontinued during the screening period (3 days prior to visit 2).

         18. Subject in treatment with anticoagulants (with the exception of acetylsalicylic acid),
             methotrexate or rifampicin or antihypertensives (with the exception of
             Ca+-antagonists).

         19. Have received treatment within the last 30 days with a drug that has not received
             regulatory approval for any indication at Visit 1.

         20. Have a history of substance abuse or dependence within the past year, excluding
             nicotine and caffeine.

         21. Subject at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and
             persistent or recurrent chest infections and subjects who are permanently bed ridden
             or wheelchair bound).

         22. Subject with a history of, or suspected, demyelinating disease of the central nervous
             system (e.g. multiple sclerosis or optic neuritis).

         23. Have an autoimmune disorder (not including psoriasis).

         24. Subject that do not fully understand the EPM procedures according to investigator
             experience.

         25. Investigator site personnel directly affiliated with this study and/or their immediate
             family cannot participate. Immediate family is defined as a spouse, parent, child, or
             sibling, whether biological or legally adopted.

         26. Subject diagnosed with any condition suggestive of a secondary cause of knee OA
             including but not limited to knee trauma, septic arthritis, inflammatory joint
             disease, articular fracture, major dysplasia or congenital abnormality, ochronosis,
             acromegaly, hemochromatosis, Wilson's disease, or primary osteochondromatosis.

         27. History of surgery (including arthroscopy) in the index knee within 3 months prior to
             visit 1 or already planned surgery of the index knee at any time.

         28. History of significant prior injury to the index knee within 12 months prior to visit
             1.

         29. Subject diagnosed with Kellgren and Lawrence grade IV at the index knee.

         30. Use of lower extremity assistive devices other than a knee brace or 'shoe lift'. Use
             of a cane in the hand opposite to the index knee is acceptable.

         31. History of prior synovial fluid analysis showing a White Blood Cell count ≥ 2000 mm3
             that is indicative of a diagnosis other than OA at the index knee.

         32. Have a confounding painful condition that may interfere with assessment of the index
             knee joint. (Knee pain should be the predominant pain. Mild OA of the hands is
             allowed, for instance).

         33. History of any other musculoskeletal or arthritic condition that may affect the
             interpretation of clinical efficacy and/or safety data or otherwise contraindicates
             participation in this clinical study (i.e., currently symptomatic fractures or any
             concurrent rheumatic disease such as but not limited to fibromyalgia, rheumatoid
             arthritis, gout, pseudo-gout or Paget's disease and Reiter's syndrome are excluded).

         34. Have used corticosteroids prior to baseline:

               1. Intra-articular injection of steroids into the index knee or into any other site
                  than the index knee within the previous 3 months,

               2. Intra-muscular corticosteroid injections within the previous 3 months,

               3. Oral corticosteroids within the previous 1 month.

         35. Have initiated or changed their established physiotherapy program within the last 14
             day prior to visit 3.

         36. Have not recorded a minimum of 10 days of diary data of the last 14 days immediately
             preceding visit 3.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 40 Years old.
Subject must be at most 75 Years

Eligibility (NLI label): Entailment