Open-label Milnacipran for Persistent Knee Pain One Year After Total Knee Arthroplasty (TKA)
Condition: Knee Pain After Total Knee Arthroplasty; Osteoarthritis Pain
MeSH terms: Osteoarthritis
Intervention: Open-label flexibly dosed milnacipran
Intervention MeSH terms: Milnacipran; Levomilnacipran
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Knee; Pain; Osteoarthritis

Summary:

      The current study examines the effects of milnacipran in patients who have chronic persistent
      knee pain one year or longer after total knee arthroplasty (TKA) to evaluate for a
      pain-relieving effect.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is a male or female adult outpatient age 18 or older at the time of consent.

          2. Subject has chronic persistent pain 1 year after TKA without history of new injury,
             infection, or implant failure.

          3. Subject has VAS > or = 40 mm at screen and baseline visits.

          4. Subject has an understanding, ability and willingness to fully comply with study
             procedures and restrictions.

          5. Subject has the ability to provide written, personally signed and dated informed
             consent to participate in the study, in accordance with the International Conference
             on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable
             regulations, before completing any study-related procedures.

        Exclusion Criteria:

          1. Subjects unable to complete assessments due to language or cognitive impairment

          2. Subjects with a history of bipolar disorder or psychosis as confirmed by the Mini
             International Neuropsychiatric Interview (MINI).

          3. Subject currently has (or had a history within the last 6 months of) a drug dependence
             or substance abuse disorder according to Diagnostic and Statistical Manual of Mental
             Disorders, Fourth Edition Text Revision (DSM-IV-TR) criteria (excluding nicotine).

          4. Subjects who are currently considered a suicide risk, any subject who has previously
             made a suicide attempt or who has a prior history of or are currently demonstrating
             active suicidal ideation.

          5. Subject has any clinically significant ECG or clinically significant laboratory
             abnormality (including a positive urine drug screen) at Screening.

          6. Subject has a concurrent chronic or acute illness, disability, or other condition that
             might confound the results of safety assessments administered in the study or that
             might increase risk to the subject. Similarly, the subject will be excluded if he or
             she has any additional condition(s) that in the Investigator's opinion would prohibit
             the subject from completing the study or would not be in the best interest of the
             subject. This would include any significant illness or unstable medical condition that
             could lead to difficulty complying with the protocol.

          7. Subjects who do not agree to use adequate and reliable contraception throughout the
             study.

          8. Subject previously completed, discontinued or was withdrawn from this study.

          9. Subject has taken an investigational drug or taken part in a clinical trial within 30
             days prior to Screening.

         10. Subjects treated with antidepressant medication within 4 weeks of screening visit (6
             weeks for fluoxetine).

         11. Subjects with known sensitivity to milnacipran.

         12. Subjects with liver disease or reduced liver function

         13. Subjects with obstructive uropathies

         14. Subjects who consume alcohol in amounts viewed by the Investigator to be
             contraindicated

         15. Subjects taking monoamine oxidase inhibitors

         16. Subjects with uncontrolled narrow angle glaucoma

         17. Subjects who are pregnant, may become pregnant, or who are nursing

         18. Subjects with seizure disorders

         19. Subjects with bleeding disorders or use of other medications that may cause bleeding.