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An Efficacy and Safety Study of Acetaminophen Plus Tramadol Hydrochloride (JNS013) in Participants With Chronic Pain

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ClinicalTrials.gov Identifier: NCT00736853
Recruitment Status : Completed
First Posted : August 18, 2008
Results First Posted : September 26, 2013
Last Update Posted : September 26, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

Tracking Information
First Submitted Date  ICMJE August 14, 2008
First Posted Date  ICMJE August 18, 2008
Results First Submitted Date  ICMJE April 12, 2013
Results First Posted Date  ICMJE September 26, 2013
Last Update Posted Date September 26, 2013
Study Start Date  ICMJE June 2008
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2013)
Number of Participants With Insufficient Pain Relief After the Start of Double-Blind Period [ Time Frame: Day 28 of double-blind period ]
The pain relief was regarded as insufficient, if either of the following was met, a) the value of average pain intensity felt in daily living during the past 24 hours (Visual analog scale 24 [VAS24] ) on 2 consecutive days in double-blind period worsened greater than 15 millimeter (mm) compared with the average VAS24 during 3 days before the end of open-label period, b) when the participant asked for discontinuation of treatment with the study drug because of insufficient pain relief.
Original Primary Outcome Measures  ICMJE
 (submitted: August 15, 2008)
Time to lack of analgesic efficacy from the start of double-blind period.
Change History Complete list of historical versions of study NCT00736853 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2013)
  • Change in the Visual Analog Scale for the Last 24 Hours (VAS24) Value at the Start of the Double-Blind Period From the Baseline Value at the Start of the Open-Label Period [ Time Frame: Day 1 of open-label period and Day 1 of double-blind period ]
    Pain over the last 24 hours was assessed by using VAS score ranges from 0 mm=no pain to 100 mm=worst possible pain. An increase in score from Baseline represented disease progression and decrease represented improvement.
  • Change in the VAS24 Value From the Baseline at the Final Time Point of the Double-Blind Period [ Time Frame: Day 1 and Day 28 of double-blind period ]
    Pain over the last 24 hours was assessed by using VAS score ranges from 0 mm=no pain to 100 mm=worst possible pain. An increase in score from Baseline represented disease progression and decrease represented improvement.
  • Mean Pain Intensity (PI) Score During Open-Label Period [ Time Frame: Pre-dose and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period ]
    PI was evaluated on a 4-stage scale with a score ranging from 0 to 3, wherein 0=no pain and 3=severe pain.
  • Mean PI Score During Double-Blind Period [ Time Frame: Pre-dose and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period ]
    The PI was evaluated on a 4-stage scale with a score ranging from 0 to 3, wherein 0=no pain and 3=severe pain.
  • Mean Pain Intensity Difference (PID) During the Open-Label Period [ Time Frame: Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period ]
    The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.
  • Mean PID During the Double-Blind Period [ Time Frame: Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period ]
    The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.
  • Mean Pain Relief (PAR) Score During the Open-Label Period [ Time Frame: 2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period ]
    PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.
  • Mean PAR Score During the Double-Blind Period [ Time Frame: 2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period ]
    PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.
  • Pain Intensity Difference and Pain Relief Scores (PRID) During the Open-Label Period [ Time Frame: 2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period ]
    The PRID is defined as sum of PID and PAR Scores for each participant at each evaluation time point (at 2 and 4 hours after the dosing). The overall possible score ranges for PRID is -2=worst to 7=best. The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on a 5-stage scale score ranges from 0=no relief and 4=complete relief.
  • Pain Intensity Difference and Pain Relief Scores (PRID) During the Double-Blind Period [ Time Frame: 2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period ]
    The PRID is defined as sum of PID and PAR Scores for each participant at each evaluation time point (at 2 and 4 hours after the dosing). The overall possible score range for PRID is -2=worst to 7=best. The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on a 5-stage scale score ranges from 0=no relief and 4=complete relief.
  • Sum of Pain Intensity Difference (SPID) Score During the Open-Label Period [ Time Frame: Day 1, and Day 8 of open-label period ]
    The SPID is defined as sum of the PID at 2 and 4 hours after dosing on each evaluation day. The overall possible score ranges for SPID is -4=worst to 6=best. The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.
  • Sum of Pain Intensity Difference (SPID) Score During the Double-Blind Period [ Time Frame: Day 1, 8, 15, 22 and 28 of double-blind period ]
    The SPID is defined as sum of the PID at 2 and 4 hours after dosing on each evaluation day. The overall possible score ranges for SPID is -4=worst to 6=best. The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best.
  • Total Pain Relief (TOTPAR) Score During the Open-Label Period [ Time Frame: Day 1 and Day 8 of open-label period ]
    The TOTPAR is defined as sum of PAR at 2 hours after dosing and the PAR at 4 hours after dosing on each evaluation day. Pain relief as evaluated on 5-stage scale with a score ranging from 0=no relief and 4=complete relief. Total possible score range for TOTPAR is 0=no relief to 8=complete relief.
  • Total Pain Relief (TOTPAR) Score During the Double-Blind Period [ Time Frame: Day 1, 8, 15, 22 and 28 of double-blind period ]
    The TOTPAR is defined as sum of PAR at 2 hours after dosing and the PAR at 4 hours after dosing on each evaluation day. Pain relief as evaluated on 5-stage scale with a score ranging from 0=no relief and 4=complete relief. Total possible score range for TOTPAR is 0=no relief to 8=complete relief.
  • Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Open-Label Period [ Time Frame: Day 1, and Day 8 of open-label period ]
    The SPRID is defined as sum of PID and PAR Scores at 2 hours and 4 hours after the dosing on each evaluation day. The overall possible score ranges for SPRID is -4=worst to 14=best. The PID was calculated as PI at pre-dose on Day 1, 8 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on 5-stage scale with a score ranging from 0=no relief to 4=complete relief.
  • Sum of Pain Relief Combined With Pain Intensity Difference (SPRID) Score During the Double-Blind Period [ Time Frame: Day 1, 8, 15, 22 and 28 of double-blind period ]
    The SPRID is defined as sum of PID and PAR Scores at 2 hours and 4 hours after the dosing on each evaluation day. The overall possible score ranges for SPRID is -4=worst to 14=best. The PID was calculated as PI at pre-dose on Day 1, 8, 15, 22, 28 minus PI at post-dose time point (i.e., 2 hours and 4 hours) on Day 1, 8, 15, 22, 28 respectively. Baseline PI score ranges from 1=minor to 3=severe, post-baseline PI score ranges from 0=none to 3=severe. Total possible score range for PID: -2=worst to 3=best and PAR was evaluated based on 5-stage scale with a score ranging from 0 to 4, wherein, 0=no relief and 4=complete relief.
  • Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Total Score at Day 14 of Open-Label Period [ Time Frame: Day 1 and Day 14 of open-label period ]
    The RDQ is self-administered measure of disability caused by low back pain and consists of 24 statements. The total score ranges from 0=no disability to 24=severe disability. The higher scores indicate greater physical disability.
  • Change From Baseline in RDQ Total Score at Day 28 of Double-Blind Period [ Time Frame: Day 1 and Day 28 of double-blind period ]
    The RDQ is self-administered measure of disability caused by low back pain and consists of 24 statements. The total score ranges from 0=no disability to 24=severe disability. The higher scores indicate greater physical disability.
  • Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Questionnaire Score at Day 14 of Open-Label Period [ Time Frame: Day 1 and Day 14 of open-label period ]
    The WOMAC questionnaire is an activity of daily living (ADL) indicator for Knee Osteoarthritis and designed to capture the elements of pain, stiffness, extent of obstruction to daily activities (EODA) and general index. The score for each element ranges from 0=better ADL to 10=worse ADL.
  • Change From Baseline in WOMAC Questionnaire Score at Day 28 of Double-Blind Period [ Time Frame: Day 1 and Day 28 of double-blind period ]
    The WOMAC questionnaire is an activity of daily living (ADL) indicator for knee osteoarthritis and designed to capture the elements of pain, stiffness, extent of obstruction to daily activities (EODA) and general index. The score for each element ranges from 0=better ADL to 10=worse ADL.
  • Change From Baseline in Short Form-36 (SF-36) Score at Day 14 of Open-Label Period [ Time Frame: Day 1 and Day 14 of open-label period ]
    The SF-36 is a survey of participant health and quality of life. It consists of 8 sub-scales, which are the weighted sums of the questions in their section. The 8 sub-scales are: physical functioning, role-physical, role-emotional, general health, social functioning, bodily pain, vitality, mental health. Each item is scored on a scale ranging from 0-100. Higher score defines a more favorable health status or a better mental status.
  • Change From Baseline in SF-36 at Day 28 of Double-Blind Period [ Time Frame: Day 1 and Day 28 of double-blind period ]
    The SF-36 is a survey of participant health and quality of life. It consists of 8 sub-scales, which are the weighted sums of the questions in their section. The 8 sub-scales are: physical functioning, role-physical, role-emotional, general health, social functioning, bodily pain, vitality, mental health. Each item is scored on a scale ranging from 0-100. Higher score defines a more favorable health status or a better mental status.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2008)
VAS24 changes and the time course changes, pain intensity difference (PID) and the time course changes, time course changes of pain relief rating (PAR), time course changes of sum of PID and PAR, sum of PIDs at each assessment point, etc.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Acetaminophen Plus Tramadol Hydrochloride (JNS013) in Participants With Chronic Pain
Official Title  ICMJE A Phase 3 Study of JNS013 in Patients With Chronic Pain
Brief Summary The purpose of this study is to evaluate the efficacy and safety of tramadol hydrochloride plus acetaminophen (JNS013) in participants with chronic pain accompanied by osteoarthritis (a progressive and degenerative joint disease, in which the joints become painful and stiff) of the knee or low back pain (acute or chronic pain in the lumbar or sacral regions) which cannot be controlled sufficiently with non-steriodal anti-inflammatory drugs (NSAIDs).
Detailed Description This is a multi-center (when more than one hospital or medical school team work on a medical research study), double-blind (test or experiment in which neither the person giving the treatment nor the participant knows which treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel group comparison study. The total duration of the study will be 11 weeks and consists of 4 periods; a pre-observation period (4 weeks), open-label period (2 weeks), double-blind period (4 weeks) and follow-up period (1 week). Participants will receive tramadol hydrochloride plus acetaminophen tablets orally 4 times daily for 2 weeks with no less than 4-hour intervals (up to 8 tablets per day) during the open-label period and the dose will be fixed for each participant in the latter 1 week. During the double-period participants will receive tramadol hydrochloride plus acetaminophen tablets or placebo at the same dose as used for the latter 1 week of the open-label period for up to 4 weeks. Efficacy will be primarily evaluated by number of participants with insufficient pain relief after the start of double-blind period. Participant's safety will be monitored throughout the study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pain
Intervention  ICMJE
  • Drug: Tramadol Hydrochloride Plus Acetaminophen (Open-Label)
    Fixed dose combination of tramadol 37.5 milligram (mg)/acetaminophen 325 mg, 1 or 2 tablets 4 times daily will be given for one week; dose level will be fixed for each participant during the second week based on analgesic efficacy and tolerability (maximum daily dose will be 8 tablets).
  • Drug: Tramadol Hydrochloride Plus Acetaminophen (Double-Blind)
    Fixed dose combination of tramadol 37.5 mg/acetaminophen 325 mg, 1 or 2 tablets (same dose [number of tablets] as that for the second week in the open-label period) will be given 4 times daily up to 4 weeks.
  • Drug: Placebo (Double-Blind)
    Matching placebo will be given up to 4 weeks.
Study Arms  ICMJE
  • Experimental: Tramadol Hydrochloride Plus Acetaminophen (Open-Label)
    Intervention: Drug: Tramadol Hydrochloride Plus Acetaminophen (Open-Label)
  • Experimental: Tramadol Hydrochloride Plus Acetaminophen (Double Blind)
    Intervention: Drug: Tramadol Hydrochloride Plus Acetaminophen (Double-Blind)
  • Placebo Comparator: Placebo (Double-Blind)
    Intervention: Drug: Placebo (Double-Blind)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2009)
321
Original Estimated Enrollment  ICMJE
 (submitted: August 15, 2008)
260
Actual Study Completion Date  ICMJE January 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants with sustention of chronic pain associated with OA or LBP for at least 3 months
  • Participants whose pain cannot be controlled sufficiently with at least 14-day continuous treatment with identical oral NSAIDs at a usual maximum dose during 3 months prior to this study
  • Outpatients
  • Ambulatory participants without need for any supportive device or assistance during daily life

Exclusion Criteria:

  • Participants with conditions for which opioids are contraindicated
  • Participants with conditions for which acetaminophen is contraindicated
  • Participants with history of convulsion or the possibility of convulsive seizure
  • Participants with concurrent, previous, or possible alcohol dependence, drug dependence, or narcotic addiction
  • Pregnant participants or those who may be pregnant, lactating mothers, and participants who wish pregnancy during the study period
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00736853
Other Study ID Numbers  ICMJE CR015112
JNS013-JPN-04
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Pharmaceutical K.K.
Study Sponsor  ICMJE Janssen Pharmaceutical K.K.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Pharmaceutical K.K. Clinical Trial Janssen Pharmaceutical K.K.
PRS Account Janssen Pharmaceutical K.K.
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP