Tapentadol (CG5503)

The primary objective of this randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows the study medication) , phase III, placebo and active controlled trial is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) Extended Release (ER) (base) at doses of 100-250 mg twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study is being conducted for registration and approval of tapentadol (CG5503) in the US and outside the US. The trial will consist of five periods: screening (to assess eligibility) , washout (3-7 days with determination of a baseline pain intensity), titration (of dose over 3 weeks to the optimal individual level) , maintenance (investigational drug intake for 12 weeks with adjustments allowed), and follow-up (2 weeks post treatment discontinuation). The study hypothesis is that the study drug will be more effective than placebo in reducing patients pain intensity. The Secondary objectives include the collection of pharmacokinetic (related to how the body uses the drug) information for dose verification. The trial objectives will be assessed by comparing the baseline pain level to the level of week 12 of the maintenance phase. This will be done by looking at the patient's pain diary information. Titrate tapentadol (CG5503) ER (extended release) 50mg to patient's optimal dose ranging between 100mg and 250mg twice a day; Oxycodone CR (controlled release) 10mg to 50mg twice a day; Placebo (no active ingredients). All doses of trial treatment will be taken orally with approximately 120 mL of water with or without food for a maximum timeframe of 15 weeks.

Inclusion criteria

• Patients diagnosed with osteoarthritis of the knee based on the American College of Rheumatology (ACR) criteria and functional capacity class of I-III
• patients taking analgesic medications for at least 3 months prior to screening and/or dissatisfied with their current therapy
• Patients requiring opioid treatment must be taking daily doses of opioid-based analgesic, equivalent to <160 mg of oral morphine
• baseline score of greater than or equal to 5 on an 11-point numerical rating scale, calculated as the average pain intensity during the last 3 days prior to randomization.

Exclusion criteria

• History of alcohol and/or drug abuse in Investigator's judgement
• history of significant liver insufficiency
• chronic hepatitis B or C, or HIV, presence of active hepatitis B or C within the past 3 months
• life-long history of seizure disorder or epilepsy
• history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated
• uncontrolled hypertension
• patients with severely impaired renal function
• patients with moderate to severly impaired hepatic function or with laboratory values reflecting inadequate hepatic function