Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study In Subjects With Osteoarthritic Pain Of The Knee

• Drug: PF-04136309
  
  125 mg capsules. Dose will be 4 capsules BID for 2 weeks for a total of 500 mg for each dosing interval.
• Drug: Placebo
  
  Placebo will be matched to PF-04136309. Dose, frequency, and duration same as PF-04136309.

• Experimental: PF-04136309
  
  Intervention: Drug: PF-04136309
• Placebo Comparator: Placebo
  
  Intervention: Drug: Placebo

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.