Evaluation of Effectiveness and Tolerability of Tapentadol Hydrochloride in Subjects With Severe Pain Due to Osteoarthritis Taking Either WHO Step I or Step II Analgesics or no Regular Analgesic

An Evaluation of the Effectiveness and Tolerability of Tapentadol Hydrochloride Prolonged Release, and Tapentadol Hydrochloride Immediate Release on Demand, in Subjects With Uncontrolled Severe Chronic Pain Due to Osteoarthritis of the Knee Taking Either WHO Step I or Step II Analgesics or no Regular Analgesics.

The main objective of the study is to evaluate the effectiveness, tolerability, and safety of tapentadol hydrochloride prolonged release in participants suffering from severe chronic pain due to osteoarthritis of the knee who are taking either WHO Step I or Step II analgesics or no regular analgesics. This is a clinical effectiveness trial designed to establish a link between anticipated clinical outcomes and the clinical practice by means of selected measures of clinical and subject-reported outcome.

The trial will compare the effectiveness of previous analgesic treatment (either WHO Step I or Step II analgesics or no regular analgesics) with that of tapentadol hydrochloride prolonged release (PR) treatment during defined periods of evaluation.

Inclusion Criteria:

1. Participants have signed an Informed Consent Form indicating that they understand the purpose of and the procedures required for the trial and are willing to participate in it.

2. Participants are men or non-pregnant, non-lactating women. Sexually active women must be postmenopausal, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization) before entry and throughout the trial. Women of childbearing potential must have a negative pregnancy test at screening.

3. Participants must be appropriately communicative to verbalize and to differentiate with regard to location and intensity of the pain.

4. Participants must be at least 40 years of age.

5. Participants must have a diagnosis of osteoarthritis of the knee based on the American College of Rheumatology (ACR) classification criteria:

   • Knee pain and
   • Radiographic osteophytes or
   • Knee pain and
   • Aged 40 years or above, and
   • Morning stiffness of less than 30 minutes of duration and
   • Crepitus on motion.

6. Participants must have pain at the reference joint which has been present for at least 3 months.

7. Participant's pain must require a strong analgesic (defined as WHO Step III) as judged by the Investigator.

8. Participants must report a rate of satisfaction with their previous analgesic regimen not exceeding "fair" on a participant satisfaction with treatment scale (5-point VRS).

9. If under regular, daily pretreatment:

   • Participants must be taking a WHO Step I or Step II analgesic medication for osteoarthritis of the knee on a daily basis for at least 2 weeks prior to the Screening Visit.
   • The Investigator considers dose increase of WHO Step I analgesics (as mono- or combination therapy) and/or continuation with or dose increase of WHO Step II analgesics inadequate for the individual participant, whatever applicable.
   • Participants must have an average pain intensity score (NRS 3) greater than 5 points during the last 3 days prior to the Screening Visit.

OR if no regular analgesic pretreatment is reported:

• Participants must have an average pain intensity score (NRS-3)greater than 6 points in the last 3 days prior to the Screening Visit and related to osteoarthritis.

Exclusion Criteria:

1. Presence of a clinically significant disease or laboratory findings that in the Investigator's opinion may affect efficacy or safety assessments.

2. Presence of active systemic or local infection, that may, in the opinion of the Investigator, affect the efficacy, quality of life/function or safety assessments.

3. History of alcohol or drug abuse, or suspicion thereof in the Investigator's judgment.

4. Presence of concomitant autoimmune inflammatory conditions.

5. Known history of or laboratory values reflecting severe renal impairment.

6. Known history of moderately or severely impaired hepatic function.

7. History of or active hepatitis B or C within the past 3 months or history of HIV infection.

8. History of seizure disorder or epilepsy.

9. Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm. Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post-traumatic amnesia lasting more than 24 h) or residual sequelae suggesting transient changes in consciousness.

10. Pregnant or breast-feeding.

11. History of allergy to, or hypersensitivity to tapentadol hydrochloride or its excipients, or contraindications related to tapentadol hydrochloride including:

    • Participants with acute or severe bronchial asthma or hypercapnia.
    • Participants who have or are suspected of having paralytic ileus.

12. Employees of the Investigator or trial site, with direct involvement in this trial or other trials under the direction of the Investigator or trial site, as well as family members of employees of the Investigator.

13. Participation in another trial concurrently or within 4 weeks prior to the Screening Visit.

14. Known to or suspected of not being able to comply with the protocol and the use of the investigational medicinal product.

15. Use of monoamine oxidase inhibitors within 14 days before the Screening Visit.

16. Non-stable dosing of selective serotonin reuptake inhibitors within 30 days before the Screening Visit (Doses must remain stable during the trial).

17. Osteoarthritis in a flare state.

18. Use of intra-articular injections of hyaluronic acid in the reference joint within 3 months before the Screening Visit.

19. Presence of conditions other than osteoarthritis of the reference joint that could confound the assessment or self-evaluation of pain, e.g., anatomical deformities, significant skin conditions such as abscess or syndromes with widespread pain such as fibromyalgia. Participants with osteoarthritis at joints other than the reference joint will not be excluded as long as the reference joint is the source of main pain and disability.

20. History and clinical signs at the reference joint of crystal-induced (e.g., gout, pseudo-gout), metabolic, infectious and autoimmune disease.

21. Any concomitant painful condition that could interfere with the participants' trial assessments or with their ability to differentiate the current joint pain from other painful conditions.

22. Any painful procedures during the trial (e.g., major surgery, including the reference joint) that may, in the opinion of the Investigator, affect the efficacy or safety assessments.

23. Pending litigation due to chronic pain or disability.

24. Intake of Step III analgesics within the 30 days prior to the Screening Visit.