A Study to Evaluate the Efficacy and Safety of CG5503 Prolonged Release (PR) in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee

• Change From Baseline of the Average Pain Intensity Overall in the 12-week Maintenance Period of the Daily Pain Intensity on an 11-point Numeric Rating Scale (NRS). [ Time Frame: Change from baseline over the 12 week Maintenance Period ] [ Designated as safety issue: No ]
  For this twice daily pain assessment, the participants were required to indicate the level of pain experienced over the previous 12 hours on an 11-point Numeric Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The lower the value the less pain in the treatment group. Negative values indicate a reduction in pain.
  
  

• Change From Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale (NRS) Over the Last Week of the Maintenance Period at Week 12. [ Time Frame: Change from Baseline to Week 12 of the Maintenance Period ] [ Designated as safety issue: No ]
  The twice daily pain assessments were averaged. The participants were to indicate their pain on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The lower the value the less pain intensity.
  
  
• Patient Global Impression of Change [ Time Frame: Baseline; End of 12 week maintenance period ] [ Designated as safety issue: No ]
  In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.
  
  
• Change From Baseline in the Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee Over the Last Week of the Maintenance Period at Week 12 [ Time Frame: Change from baseline to week 12 of the maintenance period ] [ Designated as safety issue: No ]
  Change from baseline to week 12 of Western Ontario McMaster Questionnaire (WOMAC) Global Score: WOMAC is measured with a Likert ordinal scale (the participant gives one of 5 possible answers) from 0 to 4. Higher scores indicate that a symptom is bothersome and physically disabling.
  
  
• Time to Treatment Discontinuation Due to Lack of Efficacy [ Time Frame: Baseline to week 12 of the maintenance period ] [ Designated as safety issue: No ]
  The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint.
  
  
• Change in the Health Survey Scores Form (SF-36) [ Time Frame: Change From Baseline to Week 12 of the Maintenance Period ] [ Designated as safety issue: No ]
  The Scores Form 36 (SF-36) includes several brief board questions on 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. A higher score indicates an improvement in health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state.
  
  
• EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time [ Time Frame: Comparison of Baseline to Week 12 of the Maintenance Period ] [ Designated as safety issue: No ]
  The participant scored the EuroQol-5. This is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. The positive values indicate that during the study the health status improved.
  
  
• Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. [ Time Frame: Week 12 of the maintenance period compared to baseline ] [ Designated as safety issue: No ]
  The Sleep Questionnaire addressed the following question: "How long after bedtime/lights out did you fall asleep last night(hours)?". The mean change from baseline to 12 weeks was studied. Decrease in time, measured in hours, indicates an improvement.
  
  
• Sleep Questionnaire: Amount of Time Slept in Hours [ Time Frame: Baseline to Week 12 of the maintenance period ] [ Designated as safety issue: No ]
  The Sleep Questionnaire addressed the following question: "How long did you sleep last night?". The mean change for the number of hours slept during the night before from baseline to 12 weeks was studied.
  
  
• Sleep Questionnaire: Number of Awakenings During Sleep [ Time Frame: Week 12 of the maintenance period compared with baseline ] [ Designated as safety issue: No ]
  The Sleep Questionnaire addressed the following question: "How many times did you wake up during the night?". Sleep was assessed by the subject once a week during the entire double-blind treatment period. Reported are the baseline and end of maintenance period. Generally the less the number of awakenings the better the sleep.
  
  
• Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) [ Time Frame: Week 12 of the maintenance period compared to baseline ] [ Designated as safety issue: No ]
  The Sleep Questionnaire addressed the following question: "Please rate the overall quality of your sleep last night?" The quality of sleep at baseline and prior to completion of treatment are reported. The participant can choose one of the following options: Excellent, good, fair and poor.
  
  
• Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time [ Time Frame: Change from Baseline to Week 12 of the Maintenance Period ] [ Designated as safety issue: Yes ]
  The Constipation Assessment (PAC-SYM) is a 12-item self-report questionnaire that assesses the severity of symptoms of constipation. Participants are asked "How severe have each of these symptoms been in the last two weeks?" e.g. "Pain in your stomach". There are 3 subscales: 4 questions on Abdominal symptoms, 3 on rectal symptoms and 5 on stool symptoms. Responses are rated on a 5-point Likert scale ranging from 0 (absence of symptom) to 4 (very severe symptoms). If the changes in the overall or subscale scores are positive then there is a worsening in symptoms associated with constipation.
  
  

This is a randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows which patient gets which study medication, i.e. CG5503, placebo, oxycodone), placebo and active control study. The primary objective is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) prolonged-release (PR) at doses of 100-250 mg (base) twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study 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 after end of treatment). 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 absorbs, distributes, changes and excretes the drug) information for dose verification. The efficacy objectives will be assessed by comparing the baseline pain level to the pain level during the maintenance period. This will be done by looking at the patients' pain diary information (electronic diaries).