Clinical trial NCT02248480 (phase 3, status: completed)
Conditions: osteoarthritis of the knee
ICD codes: M15.4, M15.0, M16.9, M17.9, M19.011, M19.012, M19.019
Drugs: duloxetine, placebo
SMILES: CN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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.