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A Study Comparing the Effectiveness and Safety of Extended Release (ER) Tramadol Hydrochloride (HCl)/Acetaminophen With Immediate Release (IR) Tramadol HCl/Acetaminophen in Participants With Moderate to Severe Postoperative Pain

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ClinicalTrials.gov Identifier: NCT01814878
Recruitment Status : Completed
First Posted : March 20, 2013
Results First Posted : June 20, 2013
Last Update Posted : June 20, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pain, Postoperative
Interventions Drug: Tramadol HCl/Acetaminophen ER
Drug: Tramadol HCl/Acetaminophen IR
Enrollment 320
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours. Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Period Title: Overall Study
Started 162 158
Completed 116 128
Not Completed 46 30
Reason Not Completed
Adverse Event             16             5
Withdrawal by Subject             20             16
Protocol Violation             5             5
Physician Decision             3             1
Screening failure (drop-out)             0             3
Other             2             0
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR Total
Hide Arm/Group Description Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours. Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours. Total of all reporting groups
Overall Number of Baseline Participants 162 158 320
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 162 participants 158 participants 320 participants
66.8  (6.4) 67.5  (6.6) 67.1  (6.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 162 participants 158 participants 320 participants
Female
155
  95.7%
138
  87.3%
293
  91.6%
Male
7
   4.3%
20
  12.7%
27
   8.4%
1.Primary Outcome
Title Sum of Pain Intensity Difference (SPID) at Hour 48
Hide Description The SPID is time-weighted sum of all observations of pain intensity difference (PID) collected at each measurement time point from Baseline to 48 hours. PID: Baseline pain intensity (PI) minus current PI; PI was assessed using 11-point numeric rating scale (NRS, 0=no pain to 10=worst pain imaginable). PI score ranges from 0-3 where 0=no pain and 3=severe pain. PI score of 0=NRS score of 0, PI score of 1=NRS score >=1 and <=3, PI score of 2=NRS score of >=4 and <=6 and PI score of 3=NRS score of >=7 and <=10. Total score for SPID at 48 hours (SPID48) ranges from -144 (worst) to 144 (best).
Time Frame Hour 48
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol (PP) population included all randomly assigned participants who did not violate major eligibility criteria and whose SPID was calculated with actual measurements or adjusted values at all assessment time points.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 139 127
Mean (Standard Deviation)
Unit of Measure: Units on scale
32.5  (30.7) 37.2  (23.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments Non-inferiority comparison for Tramadol Hydrochloride/Acetaminophen ER to Tramadol HCl/Acetaminophen IR was performed.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Study drug treatment group was considered non-inferior to comparator treatment group, if lower limit of the confidence interval was larger than –2.0
Statistical Test of Hypothesis P-Value 0.1648
Comments Hour 48: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.68
Confidence Interval (2-Sided) 95%
-11.29 to 1.93
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Sum of Pain Intensity Difference (SPID) at Hour 6, 12 and 24
Hide Description The SPID is time-weighted sum of all observations of PID collected at each measurement time point from Baseline to 24 hours. PID: Baseline PI minus current PI; PI was assessed using 11-point NRS, 0=no pain to 10=worst pain imaginable. PI score ranges from 0-3 where 0=no pain and 3=severe pain. PI score of 0=NRS score of 0, PI score of 1=NRS score >=1 and <=3, PI score of 2=NRS score of >=4 and <=6 and PI score of 3=NRS score of >=7 and <=10. Total score ranges from -18 (worst) to 18 (best) for SPID6, -36 (worst) to 36 (best) for SPID12 and -72 (worst) to 72 (best) for SPID24.
Time Frame Hour 6, 12, 24
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' (number of participants analyzed) specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 162 155
Mean (Standard Deviation)
Unit of Measure: Units on scale
Hour 6 3.6  (3.7) 3.9  (3.3)
Hour 12 7.0  (7.8) 8.1  (6.5)
Hour 24 14.6  (15.3) 17.6  (12.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4082
Comments Hour 6: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-1.10 to 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1720
Comments Hour 12: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.10
Confidence Interval (2-Sided) 95%
-2.68 to 0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0589
Comments Hour 24: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.99
Confidence Interval (2-Sided) 95%
-6.09 to 0.11
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Total Pain Relief (TOTPAR) Score
Hide Description Pain relief was measured on a 5-point categorical scale of 0-4 (0=no change, 1=slight relief, 2=moderate relief, 3=fair relief, 4=pain resolved completely). TOTPAR was calculated as the time-weighted sum over all pain relief up to 48 hours. Total score ranges from 0 (worst) to 24 (best) for TOTPAR6, 0 (worst) to 48 (best) for TOTPAR12, 0 (worst) to 96 (best) for TOTPAR24 and 0 (worst) to 192 (best) for TOTPAR48.
Time Frame Hour 6, 12, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 161 151
Mean (Standard Deviation)
Unit of Measure: Units on scale
Hour 6 6.0  (4.8) 6.8  (5.7)
Hour 12 12.5  (10.4) 14.7  (11.1)
Hour 24 27.1  (21.3) 31.0  (22.5)
Hour 48 55.6  (43.2) 61.7  (44.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1542
Comments Hour 6: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0714
Comments Hour 12: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1147
Comments Hour 24: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2209
Comments Hour 48: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
4.Secondary Outcome
Title Sum of Total Pain Relief and Sum of Pain Intensity Difference (SPRID)
Hide Description The SPRID is sum of SPID and TOTPAR. In SPID, PI score ranges from 0-3 where 0=no pain and 3=severe pain. PI score of 0=NRS score of 0, PI score of 1=NRS score >=1 and <= 3, PI score of 2=NRS score of >=4 and <=6 and PI score of 3=NRS score of >=7 and <=10. In TOTPAR, pain relief score ranges from 0-4 (0=no change, 1=slight relief, 2=moderate relief, 3=fair relief, 4=pain resolved completely). Total score ranges from -18 (worst) to 42 (best) for SPRID6, -36 (worst) to 84 (best) for SPRID12, -72 (worst) to 168 (best) for SPRID24 and -144 (worst) to 336 (best) for SPRID48.
Time Frame Hour 6, 12, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 161 151
Mean (Standard Deviation)
Unit of Measure: Units on scale
Hour 6 9.6  (7.3) 10.9  (8.1)
Hour 12 19.6  (15.7) 23.1  (15.2)
Hour 24 41.8  (31.6) 49.1  (30.8)
Hour 48 85.9  (64.7) 97.0  (61.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1498
Comments Hour 6: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0485
Comments Hour 12: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0404
Comments Hour 24: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1210
Comments Hour 48: P-value was calculated using Student's t-test
Method Student's t-test
Comments [Not Specified]
5.Secondary Outcome
Title Time to the First Rescue Medication Administered Because of Insufficient Pain Relief
Hide Description The time until administration of the first rescue medication (rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation) because of insufficient pain relief after administration of the study drug was recorded. Rescue medications allowed were oral or injection of tramadol HCl (intramuscular [directly into muscle] or intravenous injection [directly into vein]).
Time Frame Baseline up to Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 29 30
Mean (Standard Deviation)
Unit of Measure: Minutes
1339  (710) 1212  (853)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4216
Comments P-value was calculated using Mann-Whitney’s U test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Number of Doses of Rescue Medication Administered Because of Insufficient Pain Relief
Hide Description The frequency of the rescue medication (rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation) because of insufficient pain relief was measured after administration of the study drug. Rescue medications allowed were oral or injection of tramadol HCl (intramuscular or intravenous injection).
Time Frame Baseline up to Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 29 30
Mean (Standard Deviation)
Unit of Measure: Doses
2.1  (1.9) 1.4  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1000
Comments P-value was calculated using Mann-Whitney’s U test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Dosage of Rescue Medication Administered Because of Insufficient Pain Relief
Hide Description The dosage of the rescue medication (rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation) because of insufficient pain relief was measured after administration of the study drug. Rescue medications allowed were oral or injection of tramadol HCl (intramuscular or intravenous injection).
Time Frame Baseline up to Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 29 30
Mean (Standard Deviation)
Unit of Measure: Milligram
50.0  (0.0) 51.7  (9.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3255
Comments P-value was calculated using Mann-Whitney’s U test.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Patient Global Impression of Change (PGIC) Score
Hide Description The PGIC was used to assess the degree of participant’s overall improvement with treatment, and participants were instructed to assess how much the overall status had been improved after investigational product administration compared to baseline in 7 grades (1=Very much improved and B=Very much worsened).
Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population included all randomly assigned participants. Here, 'N' specifies those participants who were evaluable for this outcome measure.
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description:
Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours.
Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
Overall Number of Participants Analyzed 134 138
Mean (Standard Deviation)
Unit of Measure: Units on scale
2.71  (0.86) 2.60  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride (HCl)/Acetaminophen ER, Tramadol HCl/Acetaminophen IR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2848
Comments Day 3: P-value was calculated using student's t-test
Method Student's t-test
Comments [Not Specified]
Time Frame Screening up to Day 3 or early withdrawal
Adverse Event Reporting Description Safety population included all participants who received at least 1 dose of study drug. Number of participants evaluable for safety was 161 in Tramadol Hydrochloride/Acetaminophen ER arm and 153 in Tramadol HCl/Acetaminophen IR arm.
 
Arm/Group Title Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Hide Arm/Group Description Participants received 2 oral tablets of extended-release (ER) tramadol HCl (75 milligram [mg])/acetaminophen (650 mg) and 2 tablets of placebo matched to immediate-release (IR) tramadol HCl/acetaminophen orally every 12 hours up to 36 hours, and 2 tablets of placebo matched to IR tramadol HCl/acetaminophen every 6 hours up to 42 hours. Participants received 2 oral tablets of IR tramadol HCl (37.5 mg)/acetaminophen (325 mg) and 2 tablets of placebo matched to ER tramadol HCl/acetaminophen at 0, 12, 24 and 36 hours, and 2 tablets of IR tramadol HCl/acetaminophen at 6, 18, 30 and 42 hours.
All-Cause Mortality
Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Affected / at Risk (%) Affected / at Risk (%)
Total   1/161 (0.62%)   0/153 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  1/161 (0.62%)  0/153 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tramadol Hydrochloride (HCl)/Acetaminophen ER Tramadol HCl/Acetaminophen IR
Affected / at Risk (%) Affected / at Risk (%)
Total   139/161 (86.34%)   129/153 (84.31%) 
Gastrointestinal disorders     
Constipation * 1  39/161 (24.22%)  30/153 (19.61%) 
Dyspepsia * 1  11/161 (6.83%)  20/153 (13.07%) 
Nausea * 1  80/161 (49.69%)  68/153 (44.44%) 
Vomiting * 1  45/161 (27.95%)  37/153 (24.18%) 
General disorders     
Pyrexia * 1  28/161 (17.39%)  36/153 (23.53%) 
Injury, poisoning and procedural complications     
Wound secretion * 1  11/161 (6.83%)  6/153 (3.92%) 
Investigations     
Haemoglobin decreased * 1  38/161 (23.60%)  40/153 (26.14%) 
Nervous system disorders     
Dizziness * 1  17/161 (10.56%)  13/153 (8.50%) 
Headache * 1  15/161 (9.32%)  9/153 (5.88%) 
Somnolence * 1  9/161 (5.59%)  8/153 (5.23%) 
Psychiatric disorders     
Insomnia * 1  8/161 (4.97%)  1/153 (0.65%) 
Renal and urinary disorders     
Dysuria * 1  27/161 (16.77%)  24/153 (15.69%) 
Skin and subcutaneous tissue disorders     
Pruritus * 1  33/161 (20.50%)  26/153 (16.99%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 13.1
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.
Principal Investigator (PI) cannot provide any trial related information to external parties’ without mutual agreement with the Sponsor. This is valid even after the contract is cancelled.
Results Point of Contact
Name/Title: Clinical Research Director
Organization: Janssen Korea/25F, LS Yongsan Tower, 191 Hankangro 2-Ga, Yongsan-Gu, Seoul 140-702, Korea
Phone: 82-2-2094-4518
Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT01814878     History of Changes
Other Study ID Numbers: CR016636
TRAMAPPAI3005
First Submitted: March 18, 2013
First Posted: March 20, 2013
Results First Submitted: March 30, 2013
Results First Posted: June 20, 2013
Last Update Posted: June 20, 2013