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

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.