Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study In Subjects With Osteoarthritic Pain Of The Knee
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis, Knee
Intervention: PF-04136309; Placebo
Intervention description: 125 mg capsules. Dose will be 4 capsules BID for 2 weeks for a total of 500 mg for each dosing interval.; Placebo will be matched to PF-04136309. Dose, frequency, and duration same as PF-04136309.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 159.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: PF-04136309 CCR2 osteoarthritic pain knee; phase 2 placebo multicenter double-blind placebo-controlled

Summary:

      To evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics in
      patients with osteoarthritic pain of the knee. The most painful knee joint will be identified
      as the index joint at screening, and this joint will be used for all pain assessments
      throughout the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female of any race, between the ages of 18 and 75 years inclusive

          -  Female subjects must be of non-childbearing potential and have a negative pregnancy
             test at Screening.

          -  Osteoarthritis of the knee of at least 6 months duration and meeting the American
             College of Rheumatology Criteria. For radiographic criteria the Xray must have been
             taken within the last 5 years. If none is available, one should be taken and the
             diagnostic criteria confirmed prior to randomization.

          -  Willing and able to discontinue all current analgesic therapy, including OTC pain
             medications and topical analgesics for OA pain, for period beginning with washout
             phase (lasting 2 days or 5 half-lives of patient's current analgesic medication prior
             to Day -6) and continuing for the entire duration of study. As an exception,
             acetaminophen may be used for non-joint related pain at doses ≤1 g/day at the
             discretion of a qualified member of the study team.

          -  If a subject has evidence or a history of clinically significant endocrine, pulmonary,
             gastrointestinal, cardiovascular, hepatic, renal, psychiatric, or neurological
             disease, the investigator must confirm that the disease is stable (at least 4 weeks)
             and under control.

          -  QTc interval ≤450 msec and a PR interval ≤210 msec on Screening ECG.

        Exclusion Criteria:

          -  Pregnant or lactating females, and females of childbearing potential.

          -  Arthroscopy performed on index knee within 1 year of screening.

          -  Active depression as defined by or meeting The Hospital Anxiety and Depression Scale
             (HADS) of >10.

          -  Unwillingness to refrain from consumption of grapefruit or grapefruit juice from 7
             days prior to the first dose of study medication until completion of the study.

          -  First degree or higher AV block, defined as PR interval >210 msecs, bundle branch
             block, fascicular block or intraventricular conduction delay or clinically relevant
             abnormality on screening ECG.

          -  Active malignancy of any type or history of a malignancy within 10 years (with the
             exception of subjects with a history of treated basal cell carcinoma).

          -  Symptomatic OA of the hip ipsilateral to index knee which the patient considers more
             painful than the knee.

          -  Use of prohibited medications as listed below, in the absence of appropriate washout
             period. The following analgesic agents must be discontinued within 48 hours or 5 half
             lives of the analgesic being washed out prior to the baseline period (Day -6 to Day
             0);

               -  NSAIDs and selective COX-2 inhibitors;

               -  Acetaminophen ( as an exception acetaminophen may be used for non-joint related
                  pain at doses ≤1g/day);

               -  Opioids.

               -  Oral or I/M corticosteroids within 4 weeks prior to screening. I/A steroids
                  within 12 weeks prior to baseline in study joint or any other joints within 4
                  weeks prior to baseline, or I/A hyaluronic acid within 24 weeks prior to
                  baseline;

               -  Use of concomitant medications that are CYP3A inhibitors or CYP3A inducers, or
                  that are P-glycoprotein substrates within 48 hours or 5 half lives prior to
                  baseline.