Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Duloxetine 60 mg Versus Placebo in Patients With Chronic Osteoarthritis and Knee Pain in Japan
Brief Summary: The main purpose of this study is to evaluate the efficacy of the study drug known as duloxetine in participants with chronic osteoarthritis (OA) and knee pain in Japan.


Options:
A: Inclusion Criteria:

* Participants with present OA.
* Have pain for ≥ 14 days of each month for 3 months prior to study entry.
* Participants must have a score of ≥4 on the BPI average pain score before randomization.
* Females of child-bearing potential must test negative (-) on a pregnancy test.

Exclusion Criteria:

* Participants who cannot appropriately complete the daily diaries.
* Have a score change of ≧3 on BPI 24-hour average pain score between screening and baseline.
* Participants who have serious cardiovascular, hepatic, renal, endocrine, respiratory, or hematologic illness, peripheral vascular disease, or other medical condition or neuropsychiatric conditions or clinically significant laboratory abnormalities or electrocardiographic abnormalities.
* Participants who have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) higher than 100 international units per liter (IU/L) or total bilirubin higher than 1.6 milligrams/deciliter (mg/dL).
* Participants who have serum creatinine level higher than 2.0 mg/dL, or had renal transplantation or are receiving renal dialysis.
* Participants who have a diagnosis of inflammatory arthritis (that is, rheumatoid arthritis) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis and Type 1 diabetes).
* Participants who have any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
* Participants who have major depressive disorder as determined using depression module of the Mini-International Neuropsychiatric Interview (M.I.N.I.).
* Participants who have uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension.
* Participants who have received intrarticular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 1 month.
* Participants who have had knee arthroscopy of the index knee within the past year or joint replacement of the index knee or osteotomy at anytime.
* Participants who have end-stage osteoarthritis or surgery planned during the trial for the index joint.
* Participants have a prior synovial fluid analysis showing a white blood cell (WBC) ≥2000 cubic millimeters (mm3) that is indicative of a diagnosis other than OA.
* Participants taking any excluded medications that cannot be discontinued.
* Participants anticipated by the investigator to require use of nonsteroidal anti-inflammatory drugs that include acetaminophen, opioid analgesics, or other excluded medication for the duration of the study.
* Participants treated with a monoamine oxidase inhibitor (MAoI) within 14 days prior to baseline, or those with the potential need to use MAO inhibitor during the study or within 5 days of discontinuation of investigational drug.
* Participants who answer 'yes' to any of the questions about active suicidal ideation/intent/behaviors occurring within the past month (Columbia-Suicide Severity Rating Scale, suicide ideation section-questions 4 and 5; suicidal behaviors section).
* Participants who have a history of having more than one medical allergy.
* Are non-ambulatory or require the use of crutches or a walker.
* Have frequent falls that could result in hospitalization or could compromise response to treatment.
* Have a primary painful condition that may interfere with assessment of the index joint, i.e., knee.
* Have a history of drug abuse or dependence within the past year, including alcohol and excluding nicotine and caffeine.
* Have a positive urine drug screen for any substances of abuse or excluded medication.
* Have received administration of another investigational drug within the 30 days prior to screening.
* Have had previous exposure to duloxetine or completed/withdrawn from any study investigating duloxetine.
* Pregnant participants, female participants who wish to be pregnant during the clinical study period, or participants who are breast-feeding; or male participants who wish pregnancy of the partner.
B: Inclusion Criteria:

* Age: 40-85 years
* ACR criteria for OA including Kellgren-Lawrence radiographic OA grades II-IV
* VAS pain score \>5/10 within 48 hrs of the phone screen and visit 1 (Screening)
* Knee OA for a minimum of 12 months
* Need for daily pain medication to manage symptoms of OA

Exclusion Criteria:

* Currently taking MAO inhibitors or any centrally acting drug for analgesia
* Narrow angle glaucoma
* Uncontrolled hypertension
* Co-existing inflammatory arthritis, fibromyalgia or other chronic pain state
* If a female, pregnant, trying to become pregnant, or lactating
* Major depressive disorder
* Substantial alcohol use or history of significant liver disease
* Diabetes, type 1 or type 2
* Condition in which the Investigator believes would interfere with the subject's ability to comply with study instructions, or might confound the interpretation of the study results or put the subject at undue risk
* Standard MRI safety exclusions
C: Inclusion Criteria:

* Aged 40-69
* Diagnosed with knee osteoarthritis according to the American College of Rheumatology (ACR) criteria
* Grade 2-3 knee osteoarthritis according to Kellgren-Lawrence grading system
* VAS-pain score: 4 and above
* Neuropathic Pain Diagnostic Questionnaire (DN4) score: 4 and above
* Body mass index value: 40 and below

Exclusion Criteria:

* A history of trauma or surgical operation in the knee region
* Diabetes mellitus
* Fibromyalgia
* Inflammatory rheumatic disease
* Central or peripheral neurological disorder
* Severe cardiac, pulmonary, or malignant disease
* Invasive treatment for knee last 3 months
D: Inclusion Criteria:

* Age: 45-80 years
* ACR criteria for OA including Kellgren-Lawrence radiographic OA grades II-IV
* VAS pain score \>5/10 within 48 hrs of the phone screen and visit 1 (Screening)
* Knee OA for a minimum of 12 months
* Need for daily pain medication to manage symptoms of OA

Exclusion Criteria:

Currently taking MAO inhibitors or any centrally acting drug for analgesia, depression

* Narrow angle glaucoma
* Uncontrolled hypertension
* Co-existing inflammatory arthritis, fibromyalgia or other chronic pain state.
* If a female, pregnant, trying to become pregnant, or lactating
* Major depressive disorder
* Substantial alcohol use or history of significant liver disease
* Use of MAO inhibitors, triptans, serotonin precursors (tryptophan)
* Use of potent CYP1A2 inhibitors, Thioridazine, and anti-depressants
* Diabetes, type 1 or type 2
* Condition in which the Investigator believes would interfere with the subject's ability to comply with study instructions, or might confound the interpretation of the study results or put the subject at undue risk
* MRI safety necessitates the exclusion of subjects having one or more of the following:

  * Metal fragments in the eye or face, or having worked previously in the metal industry
  * Implantation of any electronic devices such as (but not limited to) cardiac pacemakers, cardiac, defibrillators, and cochlear implants or nerve stimulators.
  * Surgery on the blood vessels of the brain
  * Claustrophobia (fear of enclosed places)
  * Piercings or tattoos
  * More than 250 lbs in weight
  * Obvious brain abnormalities

Answer: A