A Study to Evaluate Long-Term Safety of Multiple Doses of Tapentadol (CG5503) Prolonged-Release (PR) and Oxycodone Controlled-Release (CR) in Patients With Chronic Pain

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety profile of tapentadol (CG5503) PR at doses of 100 mg - 250 mg administered twice daily over a maximum one year period to patients with at least a 3-month history of low back pain, or pain caused by knee or hip osteoarthritis.

Detailed Description
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Tapentadol (CG5503) is a centrally active pain-relieving drug being investigated for the treatment of acute and chronic pain. This study is a randomized (patients are assigned different treatments based on chance in a ratio of 4 patients on tapentadol (CG5503) PR to every 1 patient on oxycodone CR), open-label (both the Investigator and the patient know what medication is allocated), active-controlled, parallel-group, multicenter study. It is designed to investigate the long-term safety (side effects during up to one year of administration) and effectiveness (level of pain control) of tapentadol (CG5503) PR compared to oxycodone CR (an opioid commonly used for relief of moderate to severe pain) taken orally. The study consisted of a screening period (up to 14 days), a washout period (3 to 7 days), and an active treatment phase with titration and maintenance (total duration of 52 weeks). The doses of both of these medications will be adjusted to give the best therapeutic benefit for the patient. A total of 1123 patients will be screened. Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. Assessments of pain relief include the pain intensity numerical rating scale, and patient global impression of change scale (PGIC). Venous blood samples will be collected for the determination of serum concentrations of tapentadol (CG5503) and oxycodone. Tapentadol (CG5503) PR is also referred to as Tapentadol (CG5503) Extended Release (ER). Starting oral dose is randomly assigned to tapentadol (CG5503) PR 50 mg or oxycodone CR 10 mg twice daily (BID) x 3 days; then increase to tapentadol (CG5503)100 mg BID, oxycodone CR 20 mg BID x 4 days; during the maintenance phase upward titration may occur at a minimum of 3 day intervals in increments of tapentadol (CG5503) PR 50 mg BID or oxycodone CR 10 mg BID. The maximum doses are tapentadol (CG5503) PR 250 mg BID or oxycodone CR 50 mg BID.

Official Title
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A One-Year, Randomized, Open-Label, Parallel-Arm, Phase 3 Long-Term Safety Trial, With Controlled Adjustment of Dose, of Multiple Doses of CG5503 PR and Oxycodone CR in Subjects With Chronic Pain

Conditions
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Osteoarthritis, Hip, Osteoarthritis, Knee, Lower Back Pain, Pain

Intervention / Treatment
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* Drug: Oxycodone CR
* Drug: Tapentadol (CG5503) ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of knee or hip osteoarthritis with history of pain at the reference joint for at least 3 months or clinical diagnosis of low back pain of benign origin for at least 3 months Must be dissatisfied with their current analgesic therapy (e.g. Non-steroidal anti-inflammatory drugs NSAIDS, COX-2 inhibitors, opioids, paracetamol/acetaminophen Have a pain intensity >4 on Numerical Rating Scale Exclusion Criteria: Life-long history of seizure disorder or epilepsy Any of the following within one year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, and brain neoplasm Severe traumatic brain injury within 15 years (consisting of more than one of the following: brain contusion (injuries resulting in hemorrhage), intracranial hematoma, unconsciousness or post traumatic amnesia lasting for more than 24 hours) or residual sequelae suggesting transient changes in consciousness History of malignancy within past 2 years, with exception of a successfully treated basal cell carcinoma Presence of significant pain associated with conditions other than osteoarthritis or low back pain that could confound the assessment or self-evaluation of pain

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapentadol (CG5503)<br>Tapentadol (CG5503) extended release (ER) 100 to 250 mg twice daily (BID) for up to one year. | Drug: Tapentadol (CG5503) ER<br>* Tapentadol (CG5503) ER 50 mg oral tablet BID administered for first 3 days, 100 mg oral tablet BID administered for next 4 days, 100 to 250 mg oral tablet BID administered for the next 51 weeks.<br>* Other names: CG5503;|
| Active Comparator: Oxycodone<br>Oxycodone controlled release (CR) 20 to 50 mg twice daily (BID) for up to one year. | Drug: Oxycodone CR<br>* Oxycodone CR 10 mg oral tablet BID administered for first 3 days, 20 mg oral tablet BID administered for next 4 days, 20 to 50 mg oral tablet BID administered for the next 51 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | The number of participants who reported a TEAE during the treatment period. TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 3 days after the discontinuation of the study medication. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Pain Intensity Scores at Week 52 Using the Numerical Rating Scale (NRS) | The Participants indicated the average level of pain experienced, at each study visit, over the previous 24 hours 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. Baseline was the average pain intensity scores measured prior to randomization (At Week 1). At Week 52 again the average pain intensity scores were collected and the change in scores at Week 52 from the baseline scores was considered as the change from baseline in average pain intensity scores at Week 52. | Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Pain, Low Back Pain, Hip Pain, Knee Pain, Backache, Tapentadol