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A Study to Compare Safety and Efficacy of Tramadol Hydrochloride/Acetaminophen With Gabapentin in Participants With Diabetic Neuropathy

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ClinicalTrials.gov Identifier: NCT00634543
Recruitment Status : Completed
First Posted : March 13, 2008
Results First Posted : July 16, 2013
Last Update Posted : August 12, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Korea, Ltd., Korea

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetic Neuropathy
Interventions Drug: Tramadol hydrochloride/ Acetaminophen
Drug: Gabapentin
Enrollment 162
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42. Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Period Title: Overall Study
Started 78 84
Treated 76 80
Completed 59 63
Not Completed 19 21
Reason Not Completed
Other             1             2
Protocol Violation             3             3
Adverse Event             11             11
Withdrawal by Subject             4             4
Lost to Follow-up             0             1
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin Total
Hide Arm/Group Description Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42. Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42. Total of all reporting groups
Overall Number of Baseline Participants 71 76 147
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomly assigned participants who met the eligibility criteria and had at least 1 post-baseline efficacy assessment data.
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 76 participants 147 participants
58.2  (7.4) 56.6  (9.3) 57.4  (8.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 76 participants 147 participants
Female
34
  47.9%
45
  59.2%
79
  53.7%
Male
37
  52.1%
31
  40.8%
68
  46.3%
1.Primary Outcome
Title Change From Baseline in Pain Intensity Score at Day 43
Hide Description Pain intensity was assessed on 11-point numerical rating scale ranging from 0=no pain to 10=pain as bad as you can imagine.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomly assigned participants who met the eligiblility criteria and had at least 1 post-baseline efficacy assessment data. Last observation carried forward (LOCF) was used.
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description:
Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Overall Number of Participants Analyzed 71 76
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline 6.65  (1.60) 6.30  (1.58)
Change at Day 43 3.15  (1.83) 2.76  (1.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride/ Acetaminophen, Gabapentin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non inferiority was demonstrated if lower confidence limit of 2-sided 95% CI was less than the non-inferiority margin of 1.39.
Statistical Test of Hypothesis P-Value 0.2143
Comments [Not Specified]
Method t-test, 2 sided
Comments P-value was calculated for change from baseline in pain intensity score at Day 43.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
-0.23 to 1.01
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Pain Relief
Hide Description Pain relief was assessed on a scale ranging from -1 to 4, where -1=became worse, 0=no change, 1=relieved a little, 2=relieved moderately, 3=relieved a lot and 4=completely resolved.
Time Frame Day 15, Day 29 and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomly assigned participants who met the eligiblility criteria and had at least 1 post-baseline efficacy assessment data. Last observation carried forward (LOCF) was used.
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description:
Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Overall Number of Participants Analyzed 71 76
Measure Type: Number
Unit of Measure: Percentage of Participants
Day 15: Became worse 1.4 4.0
Day 15: No change 12.7 14.5
Day 15: Relieved a little 31.0 34.2
Day 15: Relieved moderately 26.8 21.1
Day 15: Relieved a lot 26.8 26.3
Day 15: Completely resolved 1.4 0.0
Day 29: Became worse 4.2 1.3
Day 29: No change 9.9 10.5
Day 29: Relieved a little 25.4 29.0
Day 29: Relieved moderately 21.1 14.5
Day 29: Relieved a lot 38.0 44.7
Day 29: Completely resolved 1.4 0.0
Day 43: Became worse 2.8 1.3
Day 43: No change 7.0 11.8
Day 43: Relieved a little 22.5 25.0
Day 43: Relieved moderately 19.7 15.8
Day 43: Relieved a lot 46.5 42.1
Day 43: Completely resolved 1.4 4.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride/ Acetaminophen, Gabapentin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7539
Comments [Not Specified]
Method Chi-squared
Comments P-value was evaluated for pain relief in tramadol hydrochloride/ acetaminophen versus gabapentin groups at Day 15.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride/ Acetaminophen, Gabapentin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5905
Comments [Not Specified]
Method Chi-squared
Comments P-value was evaluated for pain relief in tramadol hydrochloride/ acetaminophen versus gabapentin groups at Day 29.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride/ Acetaminophen, Gabapentin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7407
Comments [Not Specified]
Method Chi-squared
Comments P-value was evaluated for pain relief in tramadol hydrochloride/ acetaminophen versus gabapentin groups at Day 43.
3.Secondary Outcome
Title Overall Assessment of Study Medication by Participants
Hide Description Overall assessment of study medication was done by participants. Assessment was made on a scale of -2 to 2 where, -2=very bad, -1=bad, 0=no change, 1= good and 2=very good.
Time Frame Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomly assigned participants who met the eligibility criteria and had at least 1 post-baseline efficacy assessment data. Here ‘N’ signifies number of participants who were evaluated for this outcome measure.
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description:
Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Overall Number of Participants Analyzed 67 72
Measure Type: Number
Unit of Measure: Percentage of participants
Bad 4.5 12.5
No change 29.9 29.2
Good 50.8 41.7
Very good 14.9 16.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride/ Acetaminophen, Gabapentin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3504
Comments [Not Specified]
Method Chi-squared
Comments P-value was evaluated for all categories (bad, no change, good and very good).
4.Secondary Outcome
Title Overall Assessment of Study Medication by Investigator
Hide Description Overall assessment of study medication was done by Investigator. Assessment was made on a scale of -2 to 2 where, -2=very bad, -1=bad, 0=no change, 1= good and 2=very good.
Time Frame Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomly assigned participants who met the eligibility criteria and had at least 1 post-baseline efficacy assessment data. Here ‘N’ signifies number of participants who were evaluated for this outcome measure.
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description:
Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Overall Number of Participants Analyzed 67 72
Measure Type: Number
Unit of Measure: Percentage of participants
Bad 0 2.8
No change 31.3 30.6
Good 50.8 51.4
Very good 17.9 15.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tramadol Hydrochloride/ Acetaminophen, Gabapentin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5690
Comments [Not Specified]
Method Chi-squared
Comments P-value was evaluated for all categories (bad, no change, good and very good).
5.Secondary Outcome
Title Change From Baseline in Brief Pain Inventory (BPI) Score at Day 43
Hide Description The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Pain severity score is caculated by sum of all severity items (pain worst, pain least, pain average and pain now) divided by pain now. Total score for pain severity ranges from 0=no pain to 10=extreme pain. Pain interference score was calculated by sum of all interference items (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life) score. Total score for pain interference ranges from 0=no interference to 70= interferes completely.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomly assigned participants who met the eligibility criteria and had at least 1 post-baseline efficacy assessment data. Here 'n' signifies number of participants who were evaluated for this outcome measure at a particular time point.
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description:
Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Overall Number of Participants Analyzed 71 76
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline: Pain severity score (n=68, 73) 4.5  (1.3) 4.9  (1.8)
Change at Day 43: Pain severity score (n=60, 60) 0.1  (2.3) 0.1  (1.9)
Baseline: Pain interference score (n=71, 76) 30.2  (14.8) 29.8  (14.8)
Change at Day 43:Pain interference score(n=63, 68) -11.0  (15.4) -8.8  (14.7)
6.Secondary Outcome
Title Change From Baseline in Short Form-36 (SF-36) Score at Day 43
Hide Description The SF-36 is designed to assess the health status of participants. The SF-36 includes 1 multi-item scale measuring physical health and mental health. Physical health includes physical functioning, role limitations due to physical health, pain and general health. Mantal health includes role limitations due to emotional problems, energy/fatigue, emotional well being and social functioning. Each item is scored on a 0-100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state.
Time Frame Baseline and Day 43
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomly assigned participants who met the eligibility criteria and had at least 1 post-baseline efficacy assessment data. Here 'n' signifies number of participants who were evaluated for at given time point.
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description:
Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
Overall Number of Participants Analyzed 71 76
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline: Phiysical functioning (n=71,76) 56.3  (24.1) 60.6  (24.5)
Change at Day 43: Physical functioning (n=63, 68)) 3.2  (19.7) 3.2  (19.4)
Baseline: Physical role limitation (n=71,76) 42.3  (42.8) 49.3  (41.6)
Change at Day 43:Physical role limitation(n=62,68) 13.7  (41.4) 10.7  (43.3)
Baseline: Pain (n=71,76) 49.3  (20.9) 50.8  (18.1)
Change at Day 43: Pain (n=63, 68) 15.6  (22.7) 10.4  (22.2)
Baseline: General health (n=71,76) 38.0  (20.4) 40.3  (17.8)
Change at Day 43: General health (n=63, 68) 4.6  (18.8) 4.4  (14.1)
Baseline: Emotional role limitation (n=71,76) 46.9  (44.9) 50.4  (45.7)
Change at Day43:Emotional role limitation(n=63,68) 12.7  (49.9) 18.1  (47.3)
Baseline: Energy/Fatigue (n=71,76) 39.4  (22.1) 42.6  (19.7)
Change at Day 43: Energy/Fatigue (n=63, 68) 5.7  (21.8) 10.0  (17.8)
Baseline: Emotional well-being (n=71,76) 57.2  (22.0) 61.4  (18.9)
Change at Day 43: Emotional well being (n=63, 68) 5.3  (23.3) 7.0  (16.0)
Baseline: Social functioning (n=71,76) 68.3  (23.3) 72.2  (24.5)
Change at Dya 43: Social functioning (n=63, 68) 9.9  (24.9) 5.5  (24.9)
Time Frame Baseline up to Day 43
Adverse Event Reporting Description Safety analysis population included all randomly assigned participants who received at least 1 dose of study medication.
 
Arm/Group Title Tramadol Hydrochloride/ Acetaminophen Gabapentin
Hide Arm/Group Description Participants received 1 tablet containing tramadol hydrochloride (HCl) 37.5 milligram (mg) and acetaminophen 325 mg, once daily, at bed time on Day 1 to 3, 1 tablet twice daily on Day 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there was no pain relief, the dosage were increased up to 8 tablets per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42. Participants received gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg was administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there was no pain relief, the dosage were increased up to 3600 mg per day for Day 15 to 28. The increased dose was maintained for Day 29 to 42.
All-Cause Mortality
Tramadol Hydrochloride/ Acetaminophen Gabapentin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tramadol Hydrochloride/ Acetaminophen Gabapentin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/76 (0.00%)   0/80 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Tramadol Hydrochloride/ Acetaminophen Gabapentin
Affected / at Risk (%) Affected / at Risk (%)
Total   33/76 (43.42%)   18/80 (22.50%) 
Gastrointestinal disorders     
Nausea * 1  14/76 (18.42%)  4/80 (5.00%) 
Dyspepsia * 1  6/76 (7.89%)  3/80 (3.75%) 
Nervous system disorders     
Dizziness * 1  13/76 (17.11%)  10/80 (12.50%) 
Somnolence * 1  5/76 (6.58%)  5/80 (6.25%) 
Headache * 1  6/76 (7.89%)  4/80 (5.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 16.0
The study was a non-inferiority study to demonstrate that tramadol/acetaminophen did not have poorer ffectiveness as compared to gabapentin. However this could not be demonstrated because of error in the minimum significant difference set-up.
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
Layout table for Results Point of Contact information
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
Layout table for additonal information
Responsible Party: Janssen Korea, Ltd., Korea
ClinicalTrials.gov Identifier: NCT00634543     History of Changes
Other Study ID Numbers: CR012967
ULT-KOR-06
First Submitted: March 6, 2008
First Posted: March 13, 2008
Results First Submitted: April 30, 2013
Results First Posted: July 16, 2013
Last Update Posted: August 12, 2013