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 Study of LY2828360 in Patients With Osteoarthritic Knee Pain

Eligibility criteria:
Inclusion Criteria:

          -  Are male or female participants with osteoarthritis (OA), as determined by medical
             history and physical examination. Males and females with stable medical problems that,
             in the investigator's opinion, will not significantly alter the disposition of the
             drug, will not place the participant at increased risk by participating in the study,
             and will not interfere with interpretation of the data.

               1. Male participants: agree to use a reliable method of birth control during the
                  study and for 3 months following the last dose of the investigational product

               2. Female participants: women not of child-bearing potential due to surgical
                  sterilization (at least 6 weeks post surgical bilateral oophorectomy with or
                  without hysterectomy or tubal ligation) confirmed by medical history, or
                  menopause

          -  Body weight greater than 40 kilograms (kg) and less than 120 kilograms (kg) with a
             body mass index (BMI) between 19-35 kilograms per square meter (kg/m^2) inclusive

          -  Participant with osteoarthritic knee based on disease diagnostic criteria as presented
             in the Inclusion Disease Criteria, below

          -  Blood pressure and pulse rate in supine and standing positions, within normal
             reference ranges for the population and investigator clinical research unit (CRU), or
             results with acceptable deviations that are judged to be not clinically significant by
             the investigator

          -  Have clinical laboratory test results within normal reference range for the population
             or investigator clinical research unit (CRU), or results with acceptable deviations
             that are judged to be not clinically significant by the investigator

          -  Have venous access sufficient to allow for blood sampling

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

        Inclusion Disease Criteria:

          -  Have a unilateral or bilateral osteoarthritis (OA) of the knee diagnosed according to
             the American College of Rheumatology (ACR) criteria. The clinical diagnosis of
             osteoarthritis (OA) will be confirmed by the American College of Rheumatology (ACR)
             clinical and radiographic criteria for classification of idiopathic osteoarthritis
             (OA) of the knee based upon the following criteria:

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

               2. Osteophytes (with radiographic evidence)

               3. At least 1 of the following 3 conditions: Age greater than 50, or Morning
                  stiffness less than 30 minutes, or Crepitus

          -  Have a Kellgren and Lawrence grade of I, II, III or IV

          -  Have a mean score of at least 4 (moderate) and less than or equal to 8
             (moderate-severe) on the 24-hour average pain score (0-10) (question 1) in the
             participant e-diary from screening to randomization for the knee joint during walking

          -  Discontinued use of all analgesic medications (including over-the-counter [OTC]
             analgesics/Non-Steroidal Anti-Inflammatory Drug [NSAID]) at least 2 weeks prior to
             randomization (participants are allowed limited use of analgesic medications)

        Exclusion Criteria:

          -  Are currently enrolled in, have completed or discontinued within the last 3 months
             from, a clinical trial involving an off-label investigational drug or device or are
             concurrently enrolled in any other type of medical research judged not to be
             scientifically or medically compatible with this study

          -  Have known allergies to LY2828360, related compounds or any components of the
             formulation

          -  Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the
             opinion of the investigator, increases the risks associated with participation in the
             study

          -  Have a recent or current history of cardiovascular, respiratory, hepatic, renal,
             gastrointestinal, endocrine, hematological, or neurological disorders capable of
             significantly altering the absorption, metabolism, or elimination of drugs; of
             constituting a risk when taking the study medication; or of interfering with the
             interpretation of data

          -  Have current or previous (within the past year) Axis 1 diagnosis of major depressive
             disorder, mania, bipolar disorder, psychosis, dysthymia, generalized anxiety disorder,
             alcohol or eating disorders according to the Diagnostic and Statistical Manual of
             Mental Disorders, Fourth Edition Text Revision, criteria, as determined by the
             investigator and confirmed by the Mini-International Neuropsychiatric Interview

          -  Are judged by the Principal Investigator to be clinically at suicidal risk based upon
             clinical interview

          -  Have intercurrent illness or clinically significant adverse events

          -  Have increased risk of seizures as evidenced by a history of seizures, stroke, surgery
             to the cerebral cortex, or head trauma with loss of consciousness

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

          -  Have prior renal transplant, current renal dialysis or severe renal insufficiency, or
             serum creatinine laboratory value greater than 1.5 times Upper Limit of Normal, based
             on the reference ranges of the local laboratory

          -  Have clinically significant abnormal neurological examination, especially any evidence
             of tremor or nystagmus

          -  Have a history of or symptoms suggestive of sleep apnoea

          -  Use of any known strong inducers or inhibitors of Cytochrome P450 within 30 days prior
             to enrolment.

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening

          -  Have a positive alcohol breath test at Screening

          -  Show evidence of human immunodeficiency virus infection and/or positive human HIV
             antibodies

          -  Have an active malignancy of any type or a history of malignancy (except basal cell
             carcinoma of the skin that has been excised prior to study start)

          -  Are at a high risk of infection

          -  Have an autoimmune disorder

          -  Show evidence of hepatitis C and/or positive hepatitis C antibody

          -  Show evidence of hepatitis B and/or positive hepatitis B surface antigen

          -  Are women with a positive pregnancy test or women who are lactating or child bearing

          -  Use prescription and herbal medications that cannot safely be discontinued by end of
             screening

          -  Have donated blood of more than 500 milliliters (mL) within the last 3 months

          -  Have an average weekly alcohol intake that exceeds 21 units per week (males up to age
             65) and 14 units per week (males over 65 and females), or are unwilling to refrain
             alcohol consumption for the duration of the study

          -  Are persons who have previously received the investigational product in study, have
             completed or withdrawn from this study or any other study investigation LY2828360

          -  Are taking any excluded medications (analgesic medications) and over-the- counter
             medications that cannot be discontinued at screening

          -  Show evidence or have any prior history of significant active neurological or
             psychiatric disease including depression

        Exclusion Disease Criteria:

          -  Have secondary causes of arthritis of the knee including septic arthritis,
             inflammatory joint disease, articular fracture, major dysplasias or congenital
             abnormality, ochronosis, acromegaly, hemochromatosis, Wilson's disease, and primary
             osteochondromatosis

          -  Have had lower extremity surgery (including arthroscopy of the index knee) within 6
             months prior to Screening or have surgery planned of the index knee at anytime

          -  Have had significant prior injury to the index knee within 12 months prior to
             Screening

          -  Use of lower extremity assistive devices other than a cane or knee brace (use of a
             'shoe lift' is permitted). Are non-ambulatory or require the use of crutches or a
             walker. Use of a cane in the hand opposite the index knee is acceptable

          -  Have a confounding painful condition that may interfere with assessment of the index
             joint, that is, knee

          -  Have 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

          -  Have used corticosteroid prior to baseline

          -  Have received hyaluronan injections into index knee within the previous 6 months prior
             to Treatment Phase day 3

          -  Have initiated or have changed to an established physiotherapy program within 2 weeks
             prior to Treatment Phase day 3 or during the study period An established physiotherapy
             program may be continued throughout the study period if unchanged in frequency and
             intensity

          -  Has had a prior synovial fluid analysis showing a White Blood Cell (WBC) greater than
             or equal to 2000 cubic millimeters (mm^3) that is indicative of a diagnosis other than
             OA

          -  Have started recently or changed dose regimen of any OA specific therapies (that is,
             nutraceutical products)
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