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Trial record 1 of 1 for:    NCT00486811
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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

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ClinicalTrials.gov Identifier: NCT00486811
Recruitment Status : Completed
First Posted : June 15, 2007
Results First Posted : January 11, 2011
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Grünenthal GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Pain
Knee Osteoarthritis
Interventions Drug: Tapentadol ER (100 to 250 mg twice daily)
Drug: Matching Placebo (twice daily)
Drug: Oxycodone CR (20 to 50 mg twice daily)
Enrollment 990
Recruitment Details First participant was enrolled on 04 June 2007 and the last participant out was on 18 July 2008.
Pre-assignment Details  
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description

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.

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).

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) during 15 weeks were dosed by participants (3 weeks titration and 12 weeks maintenance).

Period Title: Overall Study
Started 337 320 [1] 333 [2]
Completed 215 179 119
Not Completed 122 141 214
Reason Not Completed
Adverse Event             28             60             135
Lack of Efficacy             34             14             7
Lost to Follow-up             4             6             4
Withdrawal by Subject             33             44             58
Study drug non-compliant             5             6             3
All other             18             11             7
[1]
One participant was not eligible to be dosed.
[2]
Two participants were not eligible to be dosed.
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR Total
Hide Arm/Group Description

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.

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).

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).

Total of all reporting groups
Overall Number of Baseline Participants 337 319 331 987
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 337 participants 319 participants 331 participants 987 participants
62.2  (9.35) 62.4  (9.35) 61.8  (9.09) 62.1  (9.26)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 337 participants 319 participants 331 participants 987 participants
Between 18 and 65 years 194 194 211 599
>=65 years 143 125 120 388
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 337 participants 319 participants 331 participants 987 participants
Female
257
  76.3%
231
  72.4%
219
  66.2%
707
  71.6%
Male
80
  23.7%
88
  27.6%
112
  33.8%
280
  28.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 337 participants 319 participants 331 participants 987 participants
Portugal 8 4 3 15
Slovakia 7 8 9 24
Spain 29 23 25 77
Austria 14 12 15 41
United Kingdom 23 24 28 75
Hungary 36 35 34 105
Poland 11 11 13 35
Romania 107 103 104 314
Croatia 12 9 8 29
Germany 58 60 59 177
Latvia 24 21 24 69
Netherlands 8 9 9 26
1.Primary Outcome
Title 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).
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT), Last Observation Carried Forward (LOCF)
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 337 319 331
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-2.2  (2.06) -2.5  (2.18) -2.1  (2.17)
2.Secondary Outcome
Title 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.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). Last Observation Carried Forward (LOCF).
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 336 319 331
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-2.5  (2.30) -2.7  (2.4) -2.3  (2.36)
3.Secondary Outcome
Title Patient Global Impression of Change
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 294 248 212
Measure Type: Number
Unit of Measure: participants
Very Much Improved 33 40 25
Much Improved 94 99 65
Minimally Improved 76 61 51
No Change 59 22 30
Minimally Worse 15 9 19
Much Worse 14 14 19
Very Much Worse 3 3 3
4.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). No imputation performed.
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 218 183 114
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.0  (0.92) -1.0  (0.90) -1.1  (0.83)
5.Secondary Outcome
Title Time to Treatment Discontinuation Due to Lack of Efficacy
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Change in the Health Survey Scores Form (SF-36)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 337 319 331
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical Functioning 11.1  (23.00) 11.70  (22.91) 9.5  (18.65)
Role-Physical 18.7  (45.63) 20.8  (43.32) 13.8  (40.96)
Bodily Pain 15.4  (22.01) 19.1  (20.92) 13.9  (20.41)
General Health 6.8  (17.07) 6.8  (17.56) 4.8  (15.05)
Vitality 6.8  (21.37) 7.1  (19.40) 3.8  (18.40)
Social Functioning 7.5  (25.76) 9.2  (24.30) 4.9  (22.91)
Role-Emotional 7.9  (48.63) 11.1  (45.74) 5.0  (38.95)
Mental Health 6.3  (19.39) 3.7  (18.02) 2.7  (16.98)
7.Secondary Outcome
Title EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). Last Observation Carried Forward (LOCF).
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 337 319 331
Mean (Standard Error)
Unit of Measure: Index value
0.2  (0.02) 0.2  (0.02) 0.1  (0.01)
8.Secondary Outcome
Title Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). Last Observation Carried Forward (LOCF).
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 327 305 314
Mean (Standard Deviation)
Unit of Measure: hours
0.4  (3.68) 0.2  (2.33) 0.2  (2.14)
9.Secondary Outcome
Title Sleep Questionnaire: Amount of Time Slept in Hours
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). Last Observation Carried Forward (LOCF)
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 327 305 314
Mean (Standard Deviation)
Unit of Measure: hours
0.2  (2.10) 0.2  (2.29) 0.3  (2.01)
10.Secondary Outcome
Title Sleep Questionnaire: Number of Awakenings During Sleep
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). Last Observation Carried Forward (LOCF). The number reflects the number of participants that had the specified awakenings.
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 337 319 328
Measure Type: Number
Unit of Measure: participants
No awakening during night baseline 32 33 29
No awakening during night end point 55 44 46
1 awakening per night baseline 56 53 57
1 awakening per night end point 89 92 67
2 awakening per night baseline 102 88 85
2 awakening per night end point 84 94 89
3 awakening per night baseline 82 66 77
3 awakening per night end point 66 46 61
4 awakening per night baseline 33 39 38
4 awakening per night end point 21 22 42
5 or more awakenings per night baseline 22 26 28
5 or more awakenings per night end point 22 21 23
11.Secondary Outcome
Title Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT). Last Observation Carried Forward (LOCF). The number of participants reporting the appropriate sleep quality category are shown.
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 337 319 328
Measure Type: Number
Unit of Measure: participants
Excellent at baseline 11 8 5
Excellent at end point 10 15 19
Good at baseline 134 122 118
Good at end point 174 177 158
Fair at baseline 146 138 151
Fair at end point 124 107 125
Poor at baseline 36 37 40
Poor at end point 29 20 26
12.Secondary Outcome
Title Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time
Hide Description 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
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Safety Set
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description:

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.

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).

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).

Overall Number of Participants Analyzed 285 235 197
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Overall abdominal subscale change -0.1  (0.69) 0.1  (0.78) 0.3  (0.85)
Overall rectal subscale change 0.0  (0.52) 0.1  (0.65) 0.4  (0.81)
Overall stool subscale change 0.0  (0.74) 0.2  (0.83) 0.6  (0.97)
Overall PAC-SYM score change 0.0  (0.56) 0.1  (0.64) 0.4  (0.72)
Time Frame Baseline to week 12 of the maintenance period
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Matching Tapentadol ER Oxycodone CR
Hide Arm/Group Description

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.

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).

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).

All-Cause Mortality
Placebo Matching Tapentadol ER Oxycodone CR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Matching Tapentadol ER Oxycodone CR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/337 (1.19%)   2/319 (0.63%)   13/331 (3.93%) 
Cardiac disorders       
Atrial Fibrillation  1/337 (0.30%)  0/319 (0.00%)  3/331 (0.91%) 
Myocardial Infarction  0/337 (0.00%)  0/319 (0.00%)  0/331 (0.00%) 
Tachycardia Paroxysmal  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Ventricular Arrhythmia  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Ear and labyrinth disorders       
Vertigo  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Endocrine disorders       
Inappropriate Antidiuretic Hormone Secretion  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Gastrointestinal disorders       
Abdominal Pain Upper  0/337 (0.00%)  1/319 (0.31%)  0/331 (0.00%) 
Constipation  0/337 (0.00%)  1/319 (0.31%)  2/331 (0.60%) 
Diarrhoea  0/337 (0.00%)  1/319 (0.31%)  0/331 (0.00%) 
Vomiting  0/337 (0.00%)  1/319 (0.31%)  0/331 (0.00%) 
Colonic Polyp  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Nausea  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Infections and infestations       
Lower Respiratory Tract Infection Viral  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Injury, poisoning and procedural complications       
Foot Fracture  1/337 (0.30%)  0/319 (0.00%)  0/331 (0.00%) 
Neck injury  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Rectal Cancer  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Tumour Haemorrhage  1/337 (0.30%)  0/319 (0.00%)  0/331 (0.00%) 
Uterine Leimyoma  1/337 (0.30%)  0/319 (0.00%)  0/331 (0.00%) 
Nervous system disorders       
Syncope  0/337 (0.00%)  1/319 (0.31%)  0/331 (0.00%) 
Dizziness  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
Interstitial Lung Disease  0/337 (0.00%)  0/319 (0.00%)  1/331 (0.30%) 
1
Term from vocabulary, MedDRA (11.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Matching Tapentadol ER Oxycodone CR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   187/337 (55.49%)   214/319 (67.08%)   281/331 (84.89%) 
Ear and labyrinth disorders       
Vertigo  7/337 (2.08%)  19/319 (5.96%)  20/331 (6.04%) 
Gastrointestinal disorders       
Nausea  21/337 (6.23%)  65/319 (20.38%)  123/331 (37.16%) 
Constipation  31/337 (9.20%)  56/319 (17.55%)  114/331 (34.44%) 
Vomiting  13/337 (3.86%)  32/319 (10.03%)  86/331 (25.98%) 
Dry Mouth  7/337 (2.08%)  19/319 (5.96%)  13/331 (3.93%) 
Diarrhoea  15/337 (4.45%)  14/319 (4.39%)  26/331 (7.85%) 
Abdominal Pain Upper  20/337 (5.93%)  11/319 (3.45%)  15/331 (4.53%) 
Addominal Pain  7/337 (2.08%)  4/319 (1.25%)  18/331 (5.44%) 
General disorders       
Fatigue  11/337 (3.26%)  25/319 (7.84%)  33/331 (9.97%) 
Nervous system disorders       
Dizziness  29/337 (8.61%)  70/319 (21.94%)  88/331 (26.59%) 
Somnolence  13/337 (3.86%)  34/319 (10.66%)  48/331 (14.50%) 
Headache  31/337 (9.20%)  33/319 (10.34%)  27/331 (8.16%) 
Skin and subcutaneous tissue disorders       
Hyperhidrosis  8/337 (2.37%)  29/319 (9.09%)  27/331 (8.16%) 
Pruritus  6/337 (1.78%)  4/319 (1.25%)  36/331 (10.88%) 
1
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor and the Sponsor's designee reserves the right to review any publication pertaining to the trial at least 30 days before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
Results Point of Contact
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Name/Title: Claudia Leinweber
Organization: Grünenthal GmbH
Phone: +49 241 569 2509
EMail: claudia.leinweber@grunenthal.com
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Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT00486811    
Other Study ID Numbers: 335862
2006-005783-67 ( EudraCT Number )
First Submitted: June 14, 2007
First Posted: June 15, 2007
Results First Submitted: October 25, 2010
Results First Posted: January 11, 2011
Last Update Posted: October 18, 2019