Knee Osteoarthritis, Pain
Conditions
Keywords
Osteoarthritis, Knee, Pain Assessment, CG5503 PR, Centrally acting analgesic, Placebo, Oxycodone, Chronic Pain due to knee Osteoarthritis, Tapentadol
Brief summary
The purpose of this study is to evaluate whether tapentadol (CG5503) prolonged-release (PR) tablets at doses of 100-250 mg twice daily provide a better pain relief in patients with moderate to severe chronic pain due to osteoarthritis of the knee than a placebo (a medication without active substance). In addition the tolerability of CG5503 PR will be assessed. One third of the patients will receive CG5503 and one third will receive placebo. For further comparison one third of the patients will receive oxycodone controlled release (CR) at doses of 20-50 mg twice daily which is an active approved pain medication. Please note that tapentadol ER (Extended Release) and tapentadol PR (Prolonged Release) are identical and used interchangeably. This is due to United States of America and European naming conventions.
Detailed description
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).
Interventions
DRUGTapentadol ER (100 to 250 mg twice daily)
50, 100, 150, 200, 250 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)
DRUGMatching Placebo (twice daily)
Matching Placebo during 15 weeks (3 weeks titration and 12 weeks maintenance)
DRUGOxycodone CR (20 to 50 mg twice daily)
10, 20, 30, 40, 50 mg twice a day (BID) during 15 weeks (3 weeks titration and 12 weeks maintenance)
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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 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 \>=5 on an 11-point numeric 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 judgment; * 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 severely impaired hepatic function or with laboratory values reflecting inadequate hepatic function, * Treatment with neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants, anticonvulsants, or anti-parkinsonian drugs, treatment with any other analgesic therapy than investigational medication or rescue medication during the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | Change from baseline over the 12 week Maintenance Period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change | Baseline; End of 12 week maintenance period | 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 | Change from baseline to week 12 of the maintenance period | 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 | Baseline to week 12 of the maintenance period | The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint. |
| Change in the Health Survey Scores Form (SF-36) | Change From Baseline to Week 12 of the Maintenance Period | 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 | Comparison of Baseline to Week 12 of the Maintenance Period | 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. |
| 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. | Change from Baseline to Week 12 of the Maintenance Period | 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. |
| Sleep Questionnaire: Amount of Time Slept in Hours | Baseline to Week 12 of the maintenance period | 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 | Week 12 of the maintenance period compared with baseline | 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) | Week 12 of the maintenance period compared to baseline | 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 | Change from Baseline to Week 12 of the Maintenance Period | 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. |
| Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. | Week 12 of the maintenance period compared to baseline | 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. |
Countries
Austria, Croatia, Germany, Hungary, Italy, Latvia, Netherlands, Poland, Portugal, Romania, Slovakia, Spain, United Kingdom
Participant flow
Recruitment details
First participant was enrolled on 04 June 2007 and the last participant out was on 18 July 2008.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Drug: Matching Placebo (twice daily)
The starting dose of placebo was matched with the active treatment arms taken twice daily for the first 3 days. The dose was then increased to match the active treatments for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days as in the active treatment arms. Dose decreases were allowed without time restrictions. | 337 |
| Tapentadol ER Tapentadol ER (100 to 250 mg twice daily)
The starting dose was tapentadol ER 50 mg twice daily for 3 days. The dose was then increased to 100 mg tapentadol ER twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions.
Tapentadol ER 50, 100, 150, 200 or 250 mg twice a day (BID) during 15 weeks were dosed by participants (3 weeks titration and 12 weeks maintenance). | 319 |
| Oxycodone CR Oxycodone CR (20 to 50 mg twice daily).
The starting dose was oxycodone CR 10 mg twice daily for 3 days. The dose was then increased to 20 mg oxycodone CR twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions. Oxycodone doses were thus 10, 20, 30, 40 or 50 mg twice a day (BID) were dosed by participants during 15 weeks (3 weeks titration and 12 weeks maintenance). | 331 |
| Total | 987 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 28 | 60 | 135 |
| Overall Study | All other | 18 | 11 | 7 |
| Overall Study | Lack of Efficacy | 34 | 14 | 7 |
| Overall Study | Lost to Follow-up | 4 | 6 | 4 |
| Overall Study | Study drug non-compliant | 5 | 6 | 3 |
| Overall Study | Withdrawal by Subject | 33 | 44 | 58 |
Baseline characteristics
| Characteristic | Placebo Matching | Tapentadol ER | Oxycodone CR | Total |
|---|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.35 | 62.4 years STANDARD_DEVIATION 9.35 | 61.8 years STANDARD_DEVIATION 9.09 | 62.1 years STANDARD_DEVIATION 9.26 |
| Age, Customized >=65 years | 143 participants | 125 participants | 120 participants | 388 participants |
| Age, Customized Between 18 and 65 years | 194 participants | 194 participants | 211 participants | 599 participants |
| Region of Enrollment Austria | 14 participants | 12 participants | 15 participants | 41 participants |
| Region of Enrollment Croatia | 12 participants | 9 participants | 8 participants | 29 participants |
| Region of Enrollment Germany | 58 participants | 60 participants | 59 participants | 177 participants |
| Region of Enrollment Hungary | 36 participants | 35 participants | 34 participants | 105 participants |
| Region of Enrollment Latvia | 24 participants | 21 participants | 24 participants | 69 participants |
| Region of Enrollment Netherlands | 8 participants | 9 participants | 9 participants | 26 participants |
| Region of Enrollment Poland | 11 participants | 11 participants | 13 participants | 35 participants |
| Region of Enrollment Portugal | 8 participants | 4 participants | 3 participants | 15 participants |
| Region of Enrollment Romania | 107 participants | 103 participants | 104 participants | 314 participants |
| Region of Enrollment Slovakia | 7 participants | 8 participants | 9 participants | 24 participants |
| Region of Enrollment Spain | 29 participants | 23 participants | 25 participants | 77 participants |
| Region of Enrollment United Kingdom | 23 participants | 24 participants | 28 participants | 75 participants |
| Sex: Female, Male Female | 257 Participants | 231 Participants | 219 Participants | 707 Participants |
| Sex: Female, Male Male | 80 Participants | 88 Participants | 112 Participants | 280 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 187 / 337 | 214 / 319 | 281 / 331 |
| serious Total, serious adverse events | 4 / 337 | 2 / 319 | 13 / 331 |
Outcome results
Primary
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).
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.
Time frame: Change from baseline over the 12 week Maintenance Period
Population: Intent-to-treat (ITT), Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching | 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). | -2.2 Units on a scale | Standard Deviation 2.06 |
| Tapentadol ER | 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). | -2.5 Units on a scale | Standard Deviation 2.18 |
| Oxycodone CR | 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). | -2.1 Units on a scale | Standard Deviation 2.17 |
Secondary
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
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 frame: Change from baseline to week 12 of the maintenance period
Population: Intention to treat (ITT). No imputation performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching | 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 | -1.0 units on a scale | Standard Deviation 0.92 |
| Tapentadol ER | 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 | -1.0 units on a scale | Standard Deviation 0.9 |
| Oxycodone CR | 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 | -1.1 units on a scale | Standard Deviation 0.83 |
Secondary
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.
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.
Time frame: Change from Baseline to Week 12 of the Maintenance Period
Population: Intention to treat (ITT). Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching | 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. | -2.5 Units on a scale | Standard Deviation 2.3 |
| Tapentadol ER | 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. | -2.7 Units on a scale | Standard Deviation 2.4 |
| Oxycodone CR | 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. | -2.3 Units on a scale | Standard Deviation 2.36 |
Secondary
Change in the Health Survey Scores Form (SF-36)
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.
Time frame: Change From Baseline to Week 12 of the Maintenance Period
Population: The number indicate the available responses. For certain categories, e.g. Physical Functioning only 318 participants in the tapentadol treatment were analyzed and in the General Health analysis only 328 oxycodone- and 336 placebo-treated participants were available. Intention to treat (ITT). Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Physical Functioning | 11.1 units on a scale | Standard Deviation 23 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Role-Physical | 18.7 units on a scale | Standard Deviation 45.63 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Bodily Pain | 15.4 units on a scale | Standard Deviation 22.01 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | General Health | 6.8 units on a scale | Standard Deviation 17.07 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Vitality | 6.8 units on a scale | Standard Deviation 21.37 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Social Functioning | 7.5 units on a scale | Standard Deviation 25.76 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Role-Emotional | 7.9 units on a scale | Standard Deviation 48.63 |
| Placebo Matching | Change in the Health Survey Scores Form (SF-36) | Mental Health | 6.3 units on a scale | Standard Deviation 19.39 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Bodily Pain | 19.1 units on a scale | Standard Deviation 20.92 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Role-Emotional | 11.1 units on a scale | Standard Deviation 45.74 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | General Health | 6.8 units on a scale | Standard Deviation 17.56 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Vitality | 7.1 units on a scale | Standard Deviation 19.4 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Social Functioning | 9.2 units on a scale | Standard Deviation 24.3 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Physical Functioning | 11.70 units on a scale | Standard Deviation 22.91 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Mental Health | 3.7 units on a scale | Standard Deviation 18.02 |
| Tapentadol ER | Change in the Health Survey Scores Form (SF-36) | Role-Physical | 20.8 units on a scale | Standard Deviation 43.32 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Role-Physical | 13.8 units on a scale | Standard Deviation 40.96 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Bodily Pain | 13.9 units on a scale | Standard Deviation 20.41 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Physical Functioning | 9.5 units on a scale | Standard Deviation 18.65 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | General Health | 4.8 units on a scale | Standard Deviation 15.05 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Role-Emotional | 5.0 units on a scale | Standard Deviation 38.95 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Social Functioning | 4.9 units on a scale | Standard Deviation 22.91 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Vitality | 3.8 units on a scale | Standard Deviation 18.4 |
| Oxycodone CR | Change in the Health Survey Scores Form (SF-36) | Mental Health | 2.7 units on a scale | Standard Deviation 16.98 |
Secondary
EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time
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.
Time frame: Comparison of Baseline to Week 12 of the Maintenance Period
Population: Intention to treat (ITT). Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching | EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time | 0.2 Index value | Standard Error 0.02 |
| Tapentadol ER | EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time | 0.2 Index value | Standard Error 0.02 |
| Oxycodone CR | EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time | 0.1 Index value | Standard Error 0.01 |
Secondary
Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire)
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.
Time frame: Week 12 of the maintenance period compared to baseline
Population: Intention to treat (ITT). Last Observation Carried Forward (LOCF). The number of participants reporting the appropriate sleep quality category are shown.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Good at baseline | 134 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Excellent at baseline | 11 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Good at end point | 174 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Poor at end point | 29 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Excellent at end point | 10 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Fair at baseline | 146 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Poor at baseline | 36 participants |
| Placebo Matching | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Fair at end point | 124 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Excellent at end point | 15 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Fair at end point | 107 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Excellent at baseline | 8 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Poor at baseline | 37 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Poor at end point | 20 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Good at baseline | 122 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Good at end point | 177 participants |
| Tapentadol ER | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Fair at baseline | 138 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Good at end point | 158 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Excellent at baseline | 5 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Excellent at end point | 19 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Good at baseline | 118 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Poor at end point | 26 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Fair at baseline | 151 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Fair at end point | 125 participants |
| Oxycodone CR | Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire) | Poor at baseline | 40 participants |
Secondary
Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time
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.
Time frame: Change from Baseline to Week 12 of the Maintenance Period
Population: Safety Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matching | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall abdominal subscale change | -0.1 Units on a scale | Standard Deviation 0.69 |
| Placebo Matching | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall rectal subscale change | 0.0 Units on a scale | Standard Deviation 0.52 |
| Placebo Matching | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall stool subscale change | 0.0 Units on a scale | Standard Deviation 0.74 |
| Placebo Matching | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall PAC-SYM score change | 0.0 Units on a scale | Standard Deviation 0.56 |
| Tapentadol ER | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall PAC-SYM score change | 0.1 Units on a scale | Standard Deviation 0.64 |
| Tapentadol ER | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall abdominal subscale change | 0.1 Units on a scale | Standard Deviation 0.78 |
| Tapentadol ER | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall stool subscale change | 0.2 Units on a scale | Standard Deviation 0.83 |
| Tapentadol ER | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall rectal subscale change | 0.1 Units on a scale | Standard Deviation 0.65 |
| Oxycodone CR | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall PAC-SYM score change | 0.4 Units on a scale | Standard Deviation 0.72 |
| Oxycodone CR | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall rectal subscale change | 0.4 Units on a scale | Standard Deviation 0.81 |
| Oxycodone CR | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall stool subscale change | 0.6 Units on a scale | Standard Deviation 0.97 |
| Oxycodone CR | Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time | Overall abdominal subscale change | 0.3 Units on a scale | Standard Deviation 0.85 |
Secondary
Patient Global Impression of Change
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.
Time frame: Baseline; End of 12 week maintenance period
Population: Intention to treat (ITT). Last observation carried forward (LOCF). Assessments obtained more than one day after end of treatment were not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matching | Patient Global Impression of Change | Very Much Improved | 33 participants |
| Placebo Matching | Patient Global Impression of Change | Very Much Worse | 3 participants |
| Placebo Matching | Patient Global Impression of Change | Minimally Worse | 15 participants |
| Placebo Matching | Patient Global Impression of Change | Minimally Improved | 76 participants |
| Placebo Matching | Patient Global Impression of Change | Much Worse | 14 participants |
| Placebo Matching | Patient Global Impression of Change | Much Improved | 94 participants |
| Placebo Matching | Patient Global Impression of Change | No Change | 59 participants |
| Tapentadol ER | Patient Global Impression of Change | Minimally Worse | 9 participants |
| Tapentadol ER | Patient Global Impression of Change | Much Improved | 99 participants |
| Tapentadol ER | Patient Global Impression of Change | Minimally Improved | 61 participants |
| Tapentadol ER | Patient Global Impression of Change | No Change | 22 participants |
| Tapentadol ER | Patient Global Impression of Change | Very Much Worse | 3 participants |
| Tapentadol ER | Patient Global Impression of Change | Much Worse | 14 participants |
| Tapentadol ER | Patient Global Impression of Change | Very Much Improved | 40 participants |
| Oxycodone CR | Patient Global Impression of Change | Much Worse | 19 participants |
| Oxycodone CR | Patient Global Impression of Change | No Change | 30 participants |
| Oxycodone CR | Patient Global Impression of Change | Very Much Worse | 3 participants |
| Oxycodone CR | Patient Global Impression of Change | Much Improved | 65 participants |
| Oxycodone CR | Patient Global Impression of Change | Minimally Improved | 51 participants |
| Oxycodone CR | Patient Global Impression of Change | Minimally Worse | 19 participants |
| Oxycodone CR | Patient Global Impression of Change | Very Much Improved | 25 participants |
Secondary
Sleep Questionnaire: Amount of Time Slept in Hours
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.
Time frame: Baseline to Week 12 of the maintenance period
Population: Intention to treat (ITT). Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching | Sleep Questionnaire: Amount of Time Slept in Hours | 0.2 hours | Standard Deviation 2.1 |
| Tapentadol ER | Sleep Questionnaire: Amount of Time Slept in Hours | 0.2 hours | Standard Deviation 2.29 |
| Oxycodone CR | Sleep Questionnaire: Amount of Time Slept in Hours | 0.3 hours | Standard Deviation 2.01 |
Secondary
Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period.
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.
Time frame: Week 12 of the maintenance period compared to baseline
Population: Intention to treat (ITT). Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching | Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. | 0.4 hours | Standard Deviation 3.68 |
| Tapentadol ER | Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. | 0.2 hours | Standard Deviation 2.33 |
| Oxycodone CR | Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period. | 0.2 hours | Standard Deviation 2.14 |
Secondary
Sleep Questionnaire: Number of Awakenings During Sleep
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.
Time frame: Week 12 of the maintenance period compared with baseline
Population: Intention to treat (ITT). Last Observation Carried Forward (LOCF). The number reflects the number of participants that had the specified awakenings.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 1 awakening per night end point | 89 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 5 or more awakenings per night end point | 22 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 2 awakening per night baseline | 102 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 4 awakening per night end point | 21 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 3 awakening per night baseline | 82 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 2 awakening per night end point | 84 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | No awakening during night end point | 55 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 5 or more awakenings per night baseline | 22 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 4 awakening per night baseline | 33 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 1 awakening per night baseline | 56 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | No awakening during night baseline | 32 participants |
| Placebo Matching | Sleep Questionnaire: Number of Awakenings During Sleep | 3 awakening per night end point | 66 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 4 awakening per night end point | 22 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | No awakening during night baseline | 33 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | No awakening during night end point | 44 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 1 awakening per night baseline | 53 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 1 awakening per night end point | 92 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 2 awakening per night baseline | 88 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 2 awakening per night end point | 94 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 3 awakening per night baseline | 66 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 3 awakening per night end point | 46 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 4 awakening per night baseline | 39 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 5 or more awakenings per night baseline | 26 participants |
| Tapentadol ER | Sleep Questionnaire: Number of Awakenings During Sleep | 5 or more awakenings per night end point | 21 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 5 or more awakenings per night baseline | 28 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 3 awakening per night end point | 61 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | No awakening during night end point | 46 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 4 awakening per night end point | 42 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 4 awakening per night baseline | 38 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | No awakening during night baseline | 29 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 1 awakening per night end point | 67 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 2 awakening per night end point | 89 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 2 awakening per night baseline | 85 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 5 or more awakenings per night end point | 23 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 3 awakening per night baseline | 77 participants |
| Oxycodone CR | Sleep Questionnaire: Number of Awakenings During Sleep | 1 awakening per night baseline | 57 participants |
Secondary
Time to Treatment Discontinuation Due to Lack of Efficacy
The median time to treatment discontinuation due to lack of efficacy from baseline to endpoint.
Time frame: Baseline to week 12 of the maintenance period
Population: Intention to treat (ITT) The results for median and interquartile ranges were not estimated as an insufficient number of participants discontinued due to lack of efficacy to estimate values.