Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open Label Safety Study of COV155 in Subjects With Osteoarthritis or Chronic Low Back Pain
Brief Summary: A study to show the safety of COV155 in patients with osteoarthritis of the knee or hip or moderate to severe chronic low back pain.


Options:
A: Inclusion Criteria

* General good health, other than osteoarthritis (OA) or chronic low back pain (CLBP), based upon results of medical and surgical history and medical exam
* ≥18 years of age
* Voluntarily provide written informed consent
* Female subjects eligible if

  1. Not pregnant or lactating; not planning to become pregnant within next 60 days
  2. Surgically sterile, or 2 years postmenopausal, or practicing acceptable birth control for more than 60 days prior to Screening and use of acceptable birth control during the study and 7 days following the last dose of COV155
* Male subjects biologically capable of having children must use reliable birth control during study and 7 days after the last dose of COV155. Surgical sterilization of the subject's monogamous partner qualifies as adequate birth control
* Clinical diagnosis of one of the following

  1. OA of knee or hip for at least 1 year with moderate to severe daily pain despite chronic use of stable doses of non-steroidal anti-inflammatory drugs (NSAIDs) or other non-steroidal, non-opioid therapies or with therapy including opioids
  2. Moderate to severe CLBP for at least several hours a day for a minimum of 90 days, not due to a known malignancy, and classified as non-neuropathic, neuropathic, or symptomatic for more than 6 months after LBP surgery
  3. OA of knee and scheduled to undergo unilateral primary tricompartmental arthroplasty.
* For CLBP/OA: Average in-clinic pain score of ≥3 on 11-point (0 to 10) numerical rating scale (NRS) as an average for the last 24 hours at Screening; - Pain intensity score of ≥4 on NRS as an average for the last 24 hours at Baseline
* For TKR: 11. Post-operative pain intensity scores ≥ 4 on a 0 to 10 NRS after discontinuation of post-surgical patient controlled analgesia or intravenous pain medications; body mass index ≤ 38.0; classified as either Physical Status (PS)-1 or PS-2.

Exclusion Criteria

* Any clinically significant condition or unstable illness that precludes study participation or interferes with assessment of pain and other symptoms of CLBP or OA or would increase the risk of opioid or NSAID related adverse events
* Schizophrenia or an uncontrolled or poorly controlled major psychiatric condition or clinically significant anxiety or depression
* Active malignancy or history of malignancy within 2 years prior to Screening other than dermal or cervical squamous cell carcinoma in situ
* History of seizures (exception-pediatric febrile seizures)
* Clinically significant ECG abnormalities or uncontrolled hypo- or hypertension
* For CLBP/OA: Arthroscopic or open surgery on either the knee or hip selected as primary OA study joint within 6 months prior to Screening; - For CLBP subjects, a surgical procedure for back pain within 6 months prior to Screening, nerve or plexus block within 30 days prior to Screening or botulinum toxin injection in lower back region within 90 days prior to Screening. For OA subjects, joint injection within 30 days prior to Screening; - Surgical implants of either the knee or hip selected as the primary OA joint; history of spinal stenosis (only CLBP subjects)
* For TKR: Major prior open knee surgery on same side as arthroplasty; any other surgery/elective procedures within 4 weeks of Screening, or during study; going to rehabilitation after surgery
* Gastric reduction or gastric band surgery
* Taking opioids in equivalents to more than 20 mg hydrocodone or more than 40 mg morphine orally per day, or taking opioid medications 4 days a week or more
* Known allergy or hypersensitivity to opioids, acetaminophen or ibuprofen
* Certain lab abnormalities
* Unable to discontinue use of prohibited medications or history of substance or alcohol abuse within 2 years prior to Screening or positive urine drug test at Screening for alcohol, illicit drugs (including medical cannabis) or controlled substances other than prescribed medications
* Positive for human immunodeficiency virus, hepatitis B (surface antigen), and/or hepatitis C
* Any other chronic pain condition other than CLBP or OA that would interfere with the assessment of CLBP or OA
* Used a monoamine oxidase inhibitor, antipsychotic, or benzodiazepine within 14 days prior to Screening or started or changed doses of anticonvulsants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, or tricyclic antidepressants within 30 days prior to Screening
* Previously received COV155 in a study
* Received any investigational drugs or devices within 30 days prior to Screening
* Other criteria as specified in the protocol
B: Inclusion Criteria:

* Patients ≥40 and ≤ 80years of age
* Radiographic evidence of grade 2 or 3 osteoarthritis based on the Kellgren \& Lawrene radiographic entry criteria
* Stable osteoarthritis during 3 months
* Score of 100mm pain VAS ≤ 80mm at screening
* Score of 100mm pain VAS ≥ 50mm at baseline
* Written consent form voluntarily

Exclusion Criteria:

* Disease of spine or other Lower limb joints that could affect to evaluate the efficacy
* History of surgery or arthroscopy of the study joint within 6 months
* Trauma of study joint within 12 months
* Medication of constantly(more than 1 week) corticosteroid by oral within 3 months
* Medication of intra-articular injection within 3 months
* Diagnosed with psychical disorder, and taking medication
* History of upper gastrointestinal ulceration within 6 months
* History of upper gastrointestinal bleeding within 12 months
* Serum creatinine, ALT, AST, total bilirubin over UNL X 2.0 at screening test
* History of hypersensitivity to LAYLA, JOINS, or NSAIDs
* Participation in another clinical trials within 4 weeks
* Medication of constantly (more than 1 week) narcotic analgesics within 3 months
* Not consent about using effectual contraception method during trial
* Pregnant or lactating woman
* Investigator's judgment
C: Inclusion Criteria:

* Age 40 years or above
* Diagnosis of OA of the knee of at least 6 months duration fulfilling American College of Rheumatology criteria
* Pain in at least one knee of at least moderate severity (Likert scale \[none, mild, moderate, severe, extreme\] or VAS pain score of at least 40 \[0-100\]) on most (at least 15) days of the previous 1 month
* Taking analgesic or nonsteroidal anti-inflammatory agents for control of pain
* Documented radiographic changes of osteoarthritis of the knee (Kellgren-Lawrence grade greater than or equal to 2 at the time of screening)
* Stable on arthritis medications for previous 1 month
* Willingness and ability, with help of a caregiver if necessary, to comply with treatment and follow-up procedures
* Use of effective contraception if woman of childbearing potential
* Signed consent statement

Exclusion Criteria:

* Intra-articular (IA) corticosteroid injection of either knee within a 3 month interval immediately prior to baseline screening
* IA hyaluronates in either knee within the past 6 months
* Tidal lavage or arthroscopy of either knee within the past 12 months
* Medical condition, in the judgment of the examiner and/or study investigators, that may preclude safe participation in protocol or prevents completion of the study, such as: uncontrolled angina and/or congestive heart failure, severe chronic obstructive pulmonary disease, active treatment for cancer, major psychiatric disease, other severe systemic disease, or significant abnormalities on screening physical examination and laboratory tests that reveal clinically important abnormalities of hematological, cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or other systems
* Use of any constituent herb in HLXL within the past 3 months
* Current use of Chinese herbs for arthritis
* Use of oral prednisone in the past 30 days
* Current use of anti-coagulants (coumadin, heparin, aspirin \>325 mg per day).
* Use of any investigational drug within the past 30 days
* Inflammatory arthritis (e.g., rheumatoid or psoriatic arthritis)
* Currently participating in another intervention research study
* Unwilling to be randomized
* Plan to move residence away from the immediate area within the next 2 months
* Drug or alcohol abuse sufficient to hinder compliance with treatment or follow-up procedures
* Pregnant or lactating
* Exclusive use of a wheel chair
* Surgery in either knee in past one year
D: Inclusion Criteria:

* Participants who are scheduled to have standard primary (non-revision) unilateral (having to do with only 1 side of a structure) total knee replacement arthroplasty (TKRA-surgery to fix a joint) for non-inflammatory (no swelling, redness, and pain in tissues caused by injury or damage) degenerative joint disease (NIDJD)
* Participants who are capable of oral (having to do with the mouth) intake
* Women must be: postmenopausal (for at least 1 year), surgically sterile, abstinent (not having sexual intercourse), or practicing a highly effective method of birth control before participation in the study and who agree to continue to use the same method of birth control throughout the study in cases of women of childbearing potential
* Male participants must practice contraception, and must agree not to donate his sperms for 1 month after the last dose of study drug
* Participants who will complain of baseline pain of intensity of greater than or equal to 4 on 11-point numeric rating scale (NRS) measured within 1 hour prior to randomization (study drug assigned by chance) and a maximum of 6 hours after discontinuation of participant controlled analgesia (PCA) after at least 12 hours of application following TKRA

Exclusion Criteria:

* Participants with Illness history (severe \[very serious, life threatening\] hepatic \[having to do with the liver\] failure, severe renal \[having to do with the kidney\] failure; severe respiratory depression; risk for mental fog with head injury or brain lesions \[abnormal area of tissue, such as a wound, sore, rash, or boil\]; digestive ulcer \[sore\], severe blood abnormalities; severe cardiac insufficiency; aspirin asthma \[asthmatic attack-breathing disorder in which there is a wheezing and difficulty in breathing; caused by non-steroidal anti-inflammatory drugs\] or history of aspirin asthma; history of epilepsy \[seizure disorder\]; rheumatism, significant psychiatric disorder or taking antipsychotic drugs for psychiatric treatment)
* Administration of disallowed therapy such as: administration of oral, patch, injection or local analgesics (drug used to control pain) acting centrally (the brain and the spinal cord) or peripherally (not central) before study drug administration after completion of PCA application, surgery is conducted simultaneously in addition to TKRA, administration of monoamine oxidase (MAO) inhibitors or discontinuation of the administration within 2 weeks, tricyclic antidepressants that may increase the seizure (sudden, uncontrolled muscle spasms and loss of consciousness resulting from abnormal brain function) risk when concomitantly (given at the same time) administered, neuroleptics, or drugs that may lower the seizure threshold, use of sedatives (a medication to calm or make less anxious) other than that used for general anesthesia (loss of sensation or feeling) during surgery
* Participants who used any study drug or investigational medical device within 30 days before the start of the treatment
* Participants requiring postoperative intensive care unit (ICU) care
* Participants having hypersensitivity to tramadol or acetaminophen

Answer: A