Osteoarthritis, Hip, Osteoarthritis, Knee, Lower Back Pain, Pain
Conditions
Keywords
Osteoarthritis, Pain, Low Back Pain, Hip Pain, Knee Pain, Backache, Tapentadol
Brief summary
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
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.
Interventions
DRUGOxycodone CR
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.
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.
Sponsors
Grünenthal GmbH
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | 52 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Pain Intensity Scores at Week 52 Using the Numerical Rating Scale (NRS) | Baseline, Week 52 | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
The recruitment period for this out-patient, multicenter study occurred between 14 November 2006 & 25 July 2008.
Pre-assignment details
In this study 1123 participants passed screening, 1121 participants were randomized (2 participants were not randomized in error) & 1117 participants received at least 1 dose of study medication (4 participants did not receive study medication)
Participants by arm
| Arm | Count |
|---|---|
| Tapentadol (CG5503) Tapentadol (CG5503) extended release (ER) 100 to 250mg twice daily (BID) for up to one year | 894 |
| Oxycodone Oxycodone controlled release (CR) 20 to 50mg twice daily (BID) for up to one year. | 223 |
| Total | 1,117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 203 | 82 |
| Overall Study | All other | 28 | 3 |
| Overall Study | Lack of Efficacy | 72 | 7 |
| Overall Study | Lost to Follow-up | 40 | 7 |
| Overall Study | Resolution of Pain | 2 | 0 |
| Overall Study | Study medication non compliant | 42 | 15 |
| Overall Study | Withdrawal by Subject | 94 | 31 |
Baseline characteristics
| Characteristic | Tapentadol (CG5503) | Oxycodone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 245 Participants | 67 Participants | 312 Participants |
| Age, Categorical Between 18 and 65 years | 649 Participants | 156 Participants | 805 Participants |
| Age, Continuous | 56.8 years STANDARD_DEVIATION 12.51 | 58.1 years STANDARD_DEVIATION 11.83 | 57.0 years STANDARD_DEVIATION 12.38 |
| Region of Enrollment Europe | 210 participants | 53 participants | 263 participants |
| Region of Enrollment North America | 684 participants | 170 participants | 854 participants |
| Sex: Female, Male Female | 515 Participants | 125 Participants | 640 Participants |
| Sex: Female, Male Male | 379 Participants | 98 Participants | 477 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 766 / 894 | 202 / 223 |
| serious Total, serious adverse events | 49 / 894 | 9 / 223 |
Outcome results
Primary
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.
Time frame: 52 weeks
Population: Safety analysis set (All randomized participants who took at least one dose of study medication).
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Tapentadol (CG5503) | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 766 Participants | 2.986 |
| Oxycodone | Number of Participants With Treatment-emergent Adverse Events (TEAE) | 202 Participants | 2.47 |
Secondary
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.
Time frame: Baseline, Week 52
Population: intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapentadol (CG5503) | Change From Baseline in Average Pain Intensity Scores at Week 52 Using the Numerical Rating Scale (NRS) | -3.22 Scores on a Scale | Standard Deviation 2.664 |
| Oxycodone | Change From Baseline in Average Pain Intensity Scores at Week 52 Using the Numerical Rating Scale (NRS) | -3.14 Scores on a Scale | Standard Deviation 2.409 |