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

July 22, 2013 updated by: Janssen Pharmaceutical K.K.

A Phase 3 Study of JNS013 in Patients With Chronic Pain

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
321

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Aichi, Japan
      • Amagasaki, Japan
      • Chiba, Japan
      • Chiba N/A, Japan
      • Edogawa, Japan
      • Fukuoka, Japan
      • Fukushima, Japan
      • Iruma, Japan
      • Kagoshima, Japan
      • Kawasaki, Japan
      • Kumagaya, Japan
      • Kurume, Japan
      • Meguro, Japan
      • Minato, Japan
      • Niigata, Japan
      • Niigata N/A, Japan
      • Ohta-Ku, Japan
      • Okazaki, Japan
      • Sagamihara, Japan
      • Setagaya, Japan
      • Shibuya, Japan
      • Shinjuku-Ku, Japan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo (Double-Blind)
Drug: Placebo (Double-Blind)
Matching placebo will be given up to 4 weeks.
Experimental: Tramadol Hydrochloride Plus Acetaminophen (Open-Label)
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).
Experimental: Tramadol Hydrochloride Plus Acetaminophen (Double Blind)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Day 28 of double-blind period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Day 1 of open-label period and Day 1 of double-blind period
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.
Day 1 and Day 28 of double-blind period
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.
Pre-dose and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period
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.
Pre-dose and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period
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.
Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, and Day 8 of open-label period
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.
Pre-dose, and post-dose at 2 hours, 4 hours on Day 1, 8, 15, 22 and 28 of double-blind period
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.
2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period
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.
2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period
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.
2 hours, 4 hours post-dose on Day 1, and Day 8 of open-label period
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.
2 hours, 4 hours post-dose on Day 1, 8, 15, 22 and 28 of double-blind period
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.
Day 1, and Day 8 of open-label period
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.
Day 1, 8, 15, 22 and 28 of double-blind period
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.
Day 1 and Day 8 of open-label period
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.
Day 1, 8, 15, 22 and 28 of double-blind period
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.
Day 1, and Day 8 of open-label period
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.
Day 1, 8, 15, 22 and 28 of double-blind period
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.
Day 1 and Day 14 of open-label period
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.
Day 1 and Day 28 of double-blind period
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.
Day 1 and Day 14 of open-label period
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.
Day 1 and Day 28 of double-blind period
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.
Day 1 and Day 14 of open-label period
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.
Day 1 and Day 28 of double-blind period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Pharmaceutical K.K.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 14, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 18, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 26, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR015112
  • JNS013-JPN-04
  • NCT00736853

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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