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Compare the Efficacy and Safety of Norspan to Tramadol/Acetaminophen With Prolonged Postoperative Pain (PASSION)

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ClinicalTrials.gov Identifier: NCT01983111
Recruitment Status : Completed
First Posted : November 13, 2013
Results First Posted : July 11, 2016
Last Update Posted : July 11, 2016
Sponsor:
Information provided by (Responsible Party):
Mundipharma Korea Ltd

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pain
Interventions Drug: buprenorphine
Drug: tramadol/acetaminophen
Enrollment 136
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Period Title: Overall Study
Started 70 66
Completed 58 59
Not Completed 12 7
Reason Not Completed
Withdrawal by Subject             8             6
Adverse Event             4             0
Protocol Violation             0             1
Arm/Group Title Buprenorphine Tramadol/Acetaminophen Total
Hide Arm/Group Description

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Total of all reporting groups
Overall Number of Baseline Participants 69 65 134
Hide Baseline Analysis Population Description
* Safety set = 134
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 65 participants 134 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
26
  37.7%
38
  58.5%
64
  47.8%
>=65 years
43
  62.3%
27
  41.5%
70
  52.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 65 participants 134 participants
64.42  (10.84) 61.54  (8.96) 63.02  (10.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 65 participants 134 participants
Female
44
  63.8%
29
  44.6%
73
  54.5%
Male
25
  36.2%
36
  55.4%
61
  45.5%
1.Primary Outcome
Title Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to 6weeks After Treatment.
Hide Description NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week6/ET minus mean score at Baseline.
Time Frame baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
In the PP set, the change in the pain intensity score from Visit 1 (Baseline) to Week 6 of the investigational product administration was analyzed.
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description:

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Overall Number of Participants Analyzed 47 40
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-2.32  (1.96) -2.75  (1.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Buprenorphine, Tramadol/Acetaminophen
Comments In the Per protocol set
Type of Statistical Test Non-Inferiority or Equivalence
Comments In the PP set, for a non-inferiority test of the reduction in the pain intensity score from Visit 1 (Baseline) to Week 6 of treatment, the lower limit of the 97.5% onesided confidence interval was compared to a clinical non-inferiority margin, -1.5.
Statistical Test of Hypothesis P-Value 0.2658
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.43
Confidence Interval (2-Sided) 97.5%
-6 to 3
Parameter Dispersion
Type: Standard Deviation
Value: 1.79
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in the Pain Intensity Score (0-10 NRS) From Visit 1 (Baseline) to Week 2 of the Investigational Product Administration
Hide Description NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week 2/ET minus mean score at Baseline.
Time Frame 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
In the PP set, the reduction in the pain intensity score from Visit 1 (Baseline) to Week 2 of the investigational product administration was analyzed.
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description:

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Overall Number of Participants Analyzed 47 40
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.19  (1.61) -1.70  (1.73)
3.Secondary Outcome
Title Change in the Quality of Life (EQ-5D) Score From Visit 1 (Baseline) to Week 6 Post-dose
Hide Description

EQ-5D to measure of health related quality of life should be answered as one of 3 levels about current condition for 5 dimensions for ‘Motor capability’, ‘Self-care’, ‘Daily activities’, ‘Pain/discomfort’, ‘Depression/anxiety’ and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)).

*EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents)

EQ-5D total score could be 0.919 in maximum and -0.594 in minimum if case all index indicates the level 3. So, if EQ-5D total score closed by “1” means that the healthy condition and high quality of life.

Time Frame Baseline and at 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
In the PP set, the change in the quality of life (EQ-5D) total score from Visit 1 (Baseline) to Week 6 of the investigational product administration was analyzed.
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description:

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Overall Number of Participants Analyzed 47 40
Mean (Standard Deviation)
Unit of Measure: EQ-5D Total score
0.09  (0.19) 0.21  (0.22)
4.Secondary Outcome
Title Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS)
Hide Description The EQ VAS records the respondent’s self-rated health on a vertical, visual analogue scale where the endpoints are labelled ‘Best imaginable health state’ (score = 100) and ‘Worst imaginable health state’ (score = 0). Higher points were positive results and positive points of difference gap means improvement results.
Time Frame Baseline and at 6weeks
Hide Outcome Measure Data
Hide Analysis Population Description
In the PP set, the change in the your today health score from Visit 1 (Baseline) to Week 6 of the investigational product administration was analyzed.
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description:

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Overall Number of Participants Analyzed 47 40
Mean (Standard Deviation)
Unit of Measure: scores on a scale
14.33  (20.34) 9.08  (19.63)
5.Secondary Outcome
Title Clinical Global Impression of Change(CGIC)
Hide Description The number of patients who choose the best opinion of overall satisfaction among Clinical Global Impression of Change Scale(CGIC) among 7 point scale. Missing data was imputed by LOCF. Scores measure from 1: Very much improved to 7:very much worse.
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
In the per protocol: Analyze the within-group change in the CGIC from Baseline (Week 0) to Week 6 of the investigational product administration by using a paired t-test, and analyze the between-group difference in the change of satisfaction by using a t-test.
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description:

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Overall Number of Participants Analyzed 47 40
Mean (Standard Deviation)
Unit of Measure: Scores on 1 to 7 point
2.28  (1.21) 2.43  (1.01)
6.Secondary Outcome
Title Patient Global Impressions of Change(PGIC)
Hide Description

In the PP set, Number of participants with categorical change in overall satisfaction.

PGIC: a participant-rated instrument assessing change in participant's overall satisfaction from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse).

Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set: Analyze the within-group change in the PGIC from Baseline (Week 0) to Week 6 by using a paired t-test, and analyze the between-group difference in the change of satisfaction by using a t-test.
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description:

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Overall Number of Participants Analyzed 47 40
Mean (Standard Deviation)
Unit of Measure: Scores on 1 to 7point
2.32  (1.22) 2.45  (0.93)
Time Frame from baseline to 6 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Buprenorphine Tramadol/Acetaminophen
Hide Arm/Group Description

Patch

buprenorphine: Dosage and administration: This one patch should be attached every 7 days.

Safety was analyzed based on data for AEs, clinical laboratory tests, vital signs, and physical examination in the Safety set which consisted of 69 subjects who administered the study drug(buprenorphine) and had at least one time of safety assessment.

Oral tablet

tramadol/acetaminophen: Amount of drug ingredients

: Acetaminophen 325 mg and Tramadol hydrochloride 37.5 mg in 1 tablet of this drug.

Dosage and administration:

Adjust dose depending on a patient’s pain severity and treatment response. Starting at the initial dose of 2 tablets, usually administer 4 tablets per dose, twice daily. At a dosing interval of at least 12 hr, the daily dose should not exceed 8 tablets.

Safety was analyzed based on data for AEs, clinical laboratory tests, vital signs, and physical examination in the Safety set which consisted of 65 subjects who administered the comparator(tramadol/acetaminophen) and had at least one time of safety assessment.

All-Cause Mortality
Buprenorphine Tramadol/Acetaminophen
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Buprenorphine Tramadol/Acetaminophen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/69 (4.35%)      0/65 (0.00%)    
Infections and infestations     
Post procedural infection  2 [1]  2/69 (2.90%)  2 0/65 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1 [2]  1/69 (1.45%)  1 0/65 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
2
Term from vocabulary, MedDRA (17.1)
[1]
These cases were not related with study drug.
[2]
This case was not related with study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Buprenorphine Tramadol/Acetaminophen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/69 (26.09%)      13/65 (20.00%)    
Cardiac disorders     
Palpitations  1  0/69 (0.00%)  0 1/65 (1.54%)  1
Gastrointestinal disorders     
Constipation  1 [1]  4/69 (5.80%)  4 4/65 (6.15%)  4
Nausea  1  5/69 (7.25%)  6 3/65 (4.62%)  3
Dyspepsia  1  0/69 (0.00%)  0 2/65 (3.08%)  2
Vomiting  1  2/69 (2.90%)  2 0/65 (0.00%)  0
Diarrhoea  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Gastric disorder  1  1/69 (1.45%)  1 0/65 (0.00%)  0
General disorders     
Application site pruritus  1  3/69 (4.35%)  3 0/65 (0.00%)  0
Application site erythema  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Chills  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Oedema  1  0/69 (0.00%)  0 1/65 (1.54%)  1
Injury, poisoning and procedural complications     
Post procedural swelling  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  0/69 (0.00%)  0 3/65 (4.62%)  3
Aspartate aminotransferase increased  1  0/69 (0.00%)  0 3/65 (4.62%)  3
Haemoglobin decreased  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/69 (1.45%)  1 1/65 (1.54%)  1
Costochondritis  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Myalgia  1  1/69 (1.45%)  2 0/65 (0.00%)  0
Nervous system disorders     
Dizziness  1  2/69 (2.90%)  2 0/65 (0.00%)  0
Headache  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Paraesthesia  1  1/69 (1.45%)  1 0/65 (0.00%)  0
Post procedural infection  1  2/69 (2.90%)  2 0/65 (0.00%)  0
Herpes zoster  1  0/69 (0.00%)  0 1/65 (1.54%)  1
Skin and subcutaneous tissue disorders     
Pruritus  1  0/69 (0.00%)  0 1/65 (1.54%)  1
Pruritus generalised  1  0/69 (0.00%)  0 1/65 (1.54%)  1
Urticaria  1  0/69 (0.00%)  0 1/65 (1.54%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.1)
[1]
These cases were related with study drug & comparator.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: PhD. Miyoung Song
Organization: Mundipharma Korea Ltd.
Responsible Party: Mundipharma Korea Ltd
ClinicalTrials.gov Identifier: NCT01983111     History of Changes
Other Study ID Numbers: BUP13-KR-401
First Submitted: October 14, 2013
First Posted: November 13, 2013
Results First Submitted: September 1, 2015
Results First Posted: July 11, 2016
Last Update Posted: July 11, 2016