Patient description: The patient is a 31-year-old woman complaining of abdominal pain. The pain started last night as diffuse abdominal discomfort. She had poor appetite as well as malaise. The pain worsened in intensity and became sharp in the morning. The pain became localized to the right lower quadrant in the morning. The temperature is within the normal limits with normal vital signs. Focal tenderness and guarding were observed during palpation of the right lower quadrant. Palpation of the left lower quadrant causes pain on the right. Her lab work is remarkable for leukocytosis. Computed Tomography of the abdomen with contrast shows the presence of a distended appendix with thickened appendiceal wall without perforation, abscess or gangrene. She is a candidate for laparoscopic appendectomy under general anesthesia.

Clinical trial eligibility criteria: eligible ages (years): 18.0-80.0,  Osteoarthritis of the Knee Chronic Lower Back Pain Patient has a primary diagnosis of OA of the index knee with symptoms for at least 6 months prior to screening and patient meets American College of Rheumatology clinical classification for OA of the knee, defined by the following Knee pain and at least 3 of the following 6: 1. Age > 50 years 2. Morning stiffness < 30 minutes 3. Crepitus on active motion 4. Bony tenderness 5. Bony enlargement 6. No palpable warmth of synovium Patient has a radiographic image of the index knee (according to the minimum quality for radiographic image as set by the central radiology reader) showing evidence of OA with a Kellgren-Lawrence grade ≥2 at screening (based on central reading) Patient has moderate to severe index knee pain (pain due to OA of the knee at least 5 days per week for the last 3 months prior to screening, as determined by patient's medical history) Patient is ambulatory and the index knee must not contain any orthopedic and/or prosthetic device WOMAC pain subscale score (with a 48-hour recall period) in the index knee ≥ 4 at baseline (visit 2 predose, mean of all questions on pain subscale) WOMAC physical function subscale score ≥ 4 at baseline (visit 2 predose, mean of all questions on physical function subscale with a 48-hour recall period) Patient is willing to discontinue all current pain medications during the baseline and treatment periods (until day 57) (except for allowed rescue medications). Low dose aspirin for cardioprophylaxis is allowed Patient is compliant with daily pain recording. Compliance with diary completion will be defined as daily average pain ratings on at least 5 days of the baseline period, of which at least 3 days are in the last 4 days prior to visit 2 Male patient and their female spouse/partners who are of childbearing potential must be using a barrier method and 1 form of highly effective birth control starting at screening and continuing throughout the study period and for 90 days after the final study drug administration  Medical History / Clinical Status Patient has a history of suicide attempt or suicidal behavior. Suicidal ideation within the last 12 months (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale [C-SSRS]), or who are at significant risk to commit suicide, as judged by the investigator at screening and at the time of randomization Patient has current or prior psychosis, major depressive disorder or other clinically significant psychiatric disorder Patient has a current or prior clinically significant neurologic disease, including but not limited to peripheral neuropathy, stroke, cognitive impairment and seizure. Childhood febrile seizures are not exclusionary Patient has any clinically significant uncontrolled musculoskeletal disorder (with the exception of OA), cardiovascular, gastrointestinal, endocrinologic (diabetes mellitus is allowed if controlled [glycated hemoglobin (HbA1c) ≤ 8.0%] and no peripheral neuropathy), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, dermatologic, renal and/or other major disease Patient has an active malignancy or a history of malignancy (except for treated nonmelanoma skin cancer) within the past 5 years Patient has a history of inflammatory arthritis, (including rheumatoid arthritis or a history of RPOA, osteonecrosis or avascular necrosis of bone and/or joints), or has other diagnoses that may increase the risk of RPOA (e.g., pre-existing atrophic OA, subchondral insufficiency fracture), or severe knee malalignment or any other joint-related condition that makes the patient unsuitable for study participation (e.g., joint pain that is disproportionately severe, or which has atypical features for OA pain, should trigger further medical evaluation to rule out subchondral insufficiency fracture) Patient has findings suggestive of RPOA or increased risk for RPOA on screening radiographs of either index or non-index joints (based on central reading) Patient has a history of shoulder surgery, clinically significant trauma or current symptoms, including pain or impaired range of motion at shoulder joint Patient has a coagulopathy, is receiving anticoagulants or has been diagnosed with thrombocytopenia or a functional platelet disorder