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A Study to Compare the Frequency of Constipation Symptoms With Tapentadol Immediate Release (IR) Treatment Versus Oxycodone IR Treatment in Patients With End-stage Joint Disease

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ClinicalTrials.gov Identifier: NCT00784277
Recruitment Status : Completed
First Posted : November 3, 2008
Results First Posted : February 13, 2012
Last Update Posted : February 13, 2012
Sponsor:
Collaborator:
Grünenthal GmbH
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Joint Diseases
Arthritis
Osteoarthritis
Interventions Drug: oxycodone CR
Drug: oxycodone IR
Drug: Tapentadol ER (CG5503)
Drug: Tapentadol IR (CG5503)
Drug: placebo
Enrollment 597
Recruitment Details A total of 1000 participants were screened, 598 were randomized, 596 participants received medication in the first part of the double-blind treatment period (IR treatment phase). A total of 463 participants received medication in the second part of the double-blind treatment period (ER treatment phase).
Pre-assignment Details  
Arm/Group Title Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone Placebo ER Tapentadol ER Oxycodone CR
Hide Arm/Group Description IR Treatment : 1 capsule for 14 days IR Treatment : 50mg for 14 days IR Treatment : 75mg for 14 days IR Treatment : 10mg for 14 days ER Treatment : Tablets and capsules 2 x a day for 28 days ER Treatment : flexible dose tablets and capsules 2 x a day for 28 days (100-500mg/day) ER Treatment : flexible dose tablets and capsules 2 x a day for 28 days (20-60mg/day)
Period Title: IR Treatment
Started 148 151 154 143 0 [1] 0 [1] 0 [1]
Completed 132 134 126 100 0 0 0
Not Completed 16 17 28 43 0 0 0
Reason Not Completed
Adverse Event             4             8             19             35             0             0             0
Lack of Efficacy             4             4             1             0             0             0             0
Lost to Follow-up             1             0             1             0             0             0             0
Withdrawal by Subject             5             1             4             6             0             0             0
Resolution Of Pain             0             1             0             0             0             0             0
Other             2             3             3             2             0             0             0
[1]
"0" in ER column indicates this reporting group is not relevant to IR phase.
Period Title: ER Treatment
Started 0 [1] 0 [1] 0 [1] 0 [1] 122 [2] 250 [2] 91 [3]
Completed 0 0 0 0 113 226 76
Not Completed 0 0 0 0 9 24 15
Reason Not Completed
Adverse Event             0             0             0             0             1             7             7
Lack of Efficacy             0             0             0             0             3             4             0
Lost to Follow-up             0             0             0             0             0             2             0
Withdrawal by Subject             0             0             0             0             2             5             3
Study Medication Non-Compliant             0             0             0             0             2             3             3
Other             0             0             0             0             1             3             2
[1]
"0" in IR column indicates this reporting group is not relevant to ER phase.
[2]
10 participants who had completed IR treatment have not taken any ER treatment.
[3]
9 participants who had completed IR treatment have not taken any ER treatment.
Arm/Group Title Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone Total
Hide Arm/Group Description IR Treatment : 1 capsule for 14 days IR Treatment : 50mg capsule for 14 days IR Treatment : 75mg capsule for 14 days IR Treatment : 10mg capsule for 14 days Total of all reporting groups
Overall Number of Baseline Participants 148 151 154 143 596
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 148 participants 151 participants 154 participants 143 participants 596 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
110
  74.3%
113
  74.8%
114
  74.0%
109
  76.2%
446
  74.8%
>=65 years
38
  25.7%
38
  25.2%
40
  26.0%
34
  23.8%
150
  25.2%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 148 participants 151 participants 154 participants 143 participants 596 participants
58.8  (9.57) 58  (9.47) 58.4  (7.66) 59.4  (7.94) 58.7  (8.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 148 participants 151 participants 154 participants 143 participants 596 participants
Female
100
  67.6%
93
  61.6%
75
  48.7%
81
  56.6%
349
  58.6%
Male
48
  32.4%
58
  38.4%
79
  51.3%
62
  43.4%
247
  41.4%
Region Enroll  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 148 participants 151 participants 154 participants 143 participants 596 participants
Canada 32 36 37 34 139
USA 116 115 117 109 457
1.Primary Outcome
Title 5-Day Sum of Pain Intensity Difference (SPID5)
Hide Description SPID5 was calculated as the weighted (weights is taken as the number of hours elapsed since the previous measurement) sum of the PID collected up to 5 days. Pain intensity (PI) score is calculated as the average PI over the past 12 hours using an 11-point (0 to 10) numerical rating scale (NRS) where “0” is no pain and “10” is pain as bad as you can imagine. The difference between baseline PI at the qualifying period and current PI is pain intensity difference (PID).
Time Frame Day 1 to Day 5
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention To Treat (ITT) population : One participant who has been treated is not included in the ITT population as no baseline pain assessment was available (Arm: Tapentadol 50 mg).
Arm/Group Title Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone
Hide Arm/Group Description:
IR Treatment : 1 capsule for 14 days
IR Treatment : 50mg capsule for 14 days
IR Treatment : 75mg capsule for 14 days
IR Treatment : 10mg capsule for 14 days
Overall Number of Participants Analyzed 148 150 154 143
Mean (Standard Deviation)
Unit of Measure: Units on a scale
98.6  (134.73) 153.1  (184.07) 161.8  (187.31) 218.4  (208.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tapentadol 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments P-value is adjusted for multiplicity for comparison against placebo using Hochberg's test.
Method ANCOVA
Comments The model includes treatment and pooled center as factors and baseline pain intensity score as covariate.
Method of Estimation Estimation Parameter Difference in Least-Squares Means
Estimated Value 55.1
Confidence Interval 95%
15.11 to 95.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 20.37
Estimation Comments The 95% confidence interval is unadjusted for multiplicity.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Tapentadol 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments P-value is adjusted for multiplicity for comparison against placebo using Hochberg's test.
Method ANCOVA
Comments The model includes treatment and pooled center as factors and baseline pain intensity score as covariate.
Method of Estimation Estimation Parameter Difference in Least-Squares Means
Estimated Value 63.4
Confidence Interval 95%
23.67 to 103.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 20.23
Estimation Comments The 95% confidence interval is unadjusted for multiplicity.
2.Primary Outcome
Title Spontaneous Bowel Movements Per Week (SBMs/Week)
Hide Description The number of SBM over the 14-day IR treatment phase was determined from the Bowel Function Patient Diary and factored to enable a per week value to be used. An SBM is defined as any BM that has occurred without the use of a laxative, enema, suppository, or manual manipulation within the previous 24 hours.
Time Frame Week 1 to Week 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention To Treat (ITT) population : One participant who has been treated is not included in the ITT population as no baseline pain assessment was available (Arm: Tapentadol 50 mg).
Arm/Group Title Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone
Hide Arm/Group Description:
IR Treatment : 1 capsule for 14 days
IR Treatment : 50mg capsule for 14 days
IR Treatment : 75mg capsule for 14 days
IR Treatment : 10mg capsule for 14 days
Overall Number of Participants Analyzed 148 150 154 143
Mean (Standard Deviation)
Unit of Measure: number of stools/week
9.9  (5.16) 9.0  (4.04) 8.6  (4.65) 6.7  (5.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Oxycodone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is adjusted for multiplicity for comparison against Oxycodone using Hochberg's test.
Method ANCOVA
Comments The model includes treatment and pooled center as factors and baseline value as covariate.
Method of Estimation Estimation Parameter Difference in Least-Squares Means
Estimated Value 3.1
Confidence Interval 95%
2.22 to 4.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.46
Estimation Comments The 95% confidence interval is unadjusted for multiplicity.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tapentadol 50 mg, Oxycodone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is adjusted for multiplicity for comparison against Oxycodone using Hochberg's test.
Method ANCOVA
Comments The model includes treatment and pooled center as factors and baseline value as covariate.
Method of Estimation Estimation Parameter Difference in Least-Squares Means
Estimated Value 2.2
Confidence Interval 95%
1.34 to 3.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.45
Estimation Comments The 95% confidence interval is unadjusted for multiplicity.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tapentadol 75 mg, Oxycodone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value is adjusted for multiplicity for comparison against Oxycodone using Hochberg's test.
Method ANCOVA
Comments The model includes treatment and pooled center as factors and baseline value as covariate.
Method of Estimation Estimation Parameter Difference in Least-Squares Means
Estimated Value 1.6
Confidence Interval 95%
0.72 to 2.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.45
Estimation Comments The 95% confidence interval is unadjusted for multiplicity.
Time Frame [Not Specified]
Adverse Event Reporting Description Only participants who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. participants with Non-Serious Adverse Events.
 
Arm/Group Title Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone Placebo ER Tapentadol ER Oxycodone CR
Hide Arm/Group Description IR Treatment : 1 capsule for 14 days IR Treatment : 50mg for 14 days IR Treatment : 75mg for 14 days IR Treatment : 10mg for 14 days ER Treatment : Tablets and capsules 2 x a day for 28 days ER Treatment : flexible dose tablets and capsules 2 x a day for 28 days (100-500mg/day) ER Treatment : flexible dose tablets and capsules 2 x a day for 28 days (20-60mg/day)
All-Cause Mortality
Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone Placebo ER Tapentadol ER Oxycodone CR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone Placebo ER Tapentadol ER Oxycodone CR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/148 (0.68%)   1/151 (0.66%)   0/154 (0.00%)   1/143 (0.70%)   0/122 (0.00%)   1/250 (0.40%)   0/91 (0.00%) 
Cardiac disorders               
Arteriosclerosis coronary artery * 1  1/148 (0.68%)  0/151 (0.00%)  0/154 (0.00%)  0/143 (0.00%)  0/122 (0.00%)  0/250 (0.00%)  0/91 (0.00%) 
Myocardial infarction * 1  0/148 (0.00%)  0/151 (0.00%)  0/154 (0.00%)  1/143 (0.70%)  0/122 (0.00%)  0/250 (0.00%)  0/91 (0.00%) 
Infections and infestations               
Kidney infection * 1  0/148 (0.00%)  1/151 (0.66%)  0/154 (0.00%)  0/143 (0.00%)  0/122 (0.00%)  0/250 (0.00%)  0/91 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Pulmonary embolism * 1  0/148 (0.00%)  0/151 (0.00%)  0/154 (0.00%)  0/143 (0.00%)  0/122 (0.00%)  1/250 (0.40%)  0/91 (0.00%) 
Vascular disorders               
Deep vein thrombosis * 1  0/148 (0.00%)  0/151 (0.00%)  0/154 (0.00%)  0/143 (0.00%)  0/122 (0.00%)  1/250 (0.40%)  0/91 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Tapentadol 50 mg Tapentadol 75 mg Oxycodone Placebo ER Tapentadol ER Oxycodone CR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   48/148 (32.43%)   65/151 (43.05%)   88/154 (57.14%)   98/143 (68.53%)   23/122 (18.85%)   80/250 (32.00%)   36/91 (39.56%) 
Gastrointestinal disorders               
Nausea * 1  11/148 (7.43%)  26/151 (17.22%)  31/154 (20.13%)  57/143 (39.86%)  5/122 (4.10%)  23/250 (9.20%)  12/91 (13.19%) 
Constipation * 1  22/148 (14.86%)  21/151 (13.91%)  28/154 (18.18%)  42/143 (29.37%)  10/122 (8.20%)  37/250 (14.80%)  18/91 (19.78%) 
Vomiting * 1  1/148 (0.68%)  7/151 (4.64%)  13/154 (8.44%)  34/143 (23.78%)  5/122 (4.10%)  13/250 (5.20%)  6/91 (6.59%) 
Diarrhoea * 1  5/148 (3.38%)  4/151 (2.65%)  7/154 (4.55%)  5/143 (3.50%)  5/122 (4.10%)  13/250 (5.20%)  4/91 (4.40%) 
Dry mouth * 1  1/148 (0.68%)  4/151 (2.65%)  9/154 (5.84%)  6/143 (4.20%)  1/122 (0.82%)  3/250 (1.20%)  1/91 (1.10%) 
Nervous system disorders               
Somnolence * 1  5/148 (3.38%)  20/151 (13.25%)  14/154 (9.09%)  17/143 (11.89%)  2/122 (1.64%)  8/250 (3.20%)  2/91 (2.20%) 
Dizziness * 1  6/148 (4.05%)  17/151 (11.26%)  35/154 (22.73%)  25/143 (17.48%)  4/122 (3.28%)  5/250 (2.00%)  3/91 (3.30%) 
Headache * 1  12/148 (8.11%)  6/151 (3.97%)  7/154 (4.55%)  15/143 (10.49%)  7/122 (5.74%)  8/250 (3.20%)  4/91 (4.40%) 
Skin and subcutaneous tissue disorders               
Pruritus * 1  1/148 (0.68%)  2/151 (1.32%)  4/154 (2.60%)  13/143 (9.09%)  0/122 (0.00%)  3/250 (1.20%)  2/91 (2.20%) 
*
Indicates events were collected by non-systematic assessment
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.
Results Point of Contact
Name/Title: Senior Director, Clinical Leader
Organization: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Phone: 609-730-4537
Responsible Party: Senior Director, Clinical Leader, Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00784277     History of Changes
Other Study ID Numbers: CR014326
KF5503/41
First Submitted: October 31, 2008
First Posted: November 3, 2008
Results First Submitted: July 22, 2010
Results First Posted: February 13, 2012
Last Update Posted: February 13, 2012