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CompletedNCT00832416Updated Apr 30, 2012Results posted

A Four-Arm Study Comparing the Analgesic Efficacy and Safety of Tramadol Once a Day 100, 200 and 300 mg Versus Placebo for the Treatment of Pain Due to Osteoarthritis of the Knee

A Phase 3 interventional study of Tramadol Once A Day and Placebo in Pain and Osteoarthritis, Knee, sponsored by Labopharm Inc.. Completed. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2012-04-30.

Sponsored by Labopharm Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
565
Allocation
Randomized
Ages
40 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to compare the analgesic efficacy and safety of Tramadol Once a Day 100, 200, 300 mg and Placebo

02

Conditions studied

  • Pain
  • Osteoarthritis, Knee
03

In context

Osteoarthritis

4,398 studies on the registry are indexed under Osteoarthritis; 582 are open to participants now.

This study's enrollment of 565 is above the median of 70 across 3,440 interventional studies indexed under Osteoarthritis.

Browse Osteoarthritis studies →

Lead sponsor

Labopharm Inc. is the lead sponsor of 18 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Males or Females between the ages of 40-75 with a diagnosis of moderate to severe osteoarthritis of the knee, consistent with the American College of Rheumatology (ACR) Clinical Classification Criteria for Arthritis of the Knee:

    • Current knee pain
    • Less than 30 minutes of morning stiffness with or without crepitus on active motion.
    • Confirmation either by arthroscopy or radiologist's report (X-rays showing osteophytes, joint space narrowing or subchondral bone sclerosis {eburnation}) within five years prior to entry into the study.
  2. C-reactive protein (CRP) \< 8 ug/ml (if available at local lab) or erythrocyte sedimentation rate (ESR) \< 40 mm/hr
  3. Total WOMAC (Western Ontario and McMaster University Osteoarthritis Index) Pain Subscale Score of > 150 mm at Baseline corresponding with moderate to severe Osteoarthritis.
  4. Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials.
  5. Research Ethics Board (REB) approval of the written Informed Consent Form in Spanish or English which was signed and dated by the patient and Investigator, prior to study participation.

Exclusion criteria

Exclusion Criteria:

  1. Known rheumatoid arthritis or any other rheumatoid disease.
  2. Secondary arthritis i.e. any of the following: septic arthritis; inflammatory joint disease; gout; pseudogout; Paget's disease; joint fracture; acromegaly; fibromyalgia; Wilson's disease; ochronosis; haemochromatosis; osteochondromatosis; or collagen gene mutations.
  3. Evidence of effusion greater than 15 cubic centimetre (cc) upon physical examination of the joint at Baseline (Visit 1).
  4. Body Mass Index (BMI) ≥ 38.
  5. Major illness, requiring hospitalization during the 3 months before commencement of the screening period.
  6. The patient was unwilling to stop taking pain medication (for arthritis or other types of pain) or was unwilling to stop taking other medications for the treatment of osteoarthritis (OA).
  7. Previous failure or discontinuation (due to adverse events) of tramadol hydrochloride (HCl) therapy.
  8. Treatment within the last 3 weeks with any of the following medications: monoamine oxidase inhibitors; tricyclic antidepressants and other tricyclic compounds (e.g. cyclobenzaprine, promethazine); neuroleptics; selective serotonin reuptake inhibitors; or any other drug that reduces seizure threshold.
  9. Treatment with another investigational agent within the last 30 days.
  10. A history of seizure disorder other than Infantile Febrile Seizures.
  11. Previous or current opioid dependency.
  12. Bowel disease causing malabsorption.
  13. Pregnancy or lactating or childbearing potential and unwilling to utilize a medically approved method of contraception during participation in this clinical trial.
  14. Significant liver disease, defined as active hepatitis or elevated liver enzymes >3 times the upper boundary of the normal range.
  15. Significant renal disease, defined as creatinine clearance \<30 mL/min as estimated by the method of Levey et al., 1999.
  16. Current substance abuse or dependence, other than nicotine.
  17. Allergy or adverse reaction to tramadol or any structurally similar drugs e.g. opiates.
  18. Any other condition, that, in the opinion of the Investigators, would have adversely affected the patient's ability to complete the study or its measures.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
565 participants (actual)

Study arms

  • Experimental
    1 Tramadol Once A Day 100mg

    Drug: Tramadol Once A Day

  • Experimental
    2: Tramadol Once A Day 200mg

    Drug: Tramadol Once A Day

  • Experimental
    3: Tramadol Once A Day 300mg

    Drug: Tramadol Once A Day

  • Experimental
    4: Placebo

    Drug: Placebo

Interventions

  • DrugTramadol Once A Day

    One Tramadol Once A Day tablet at randomized dose daily.

  • DrugPlacebo

    One Placebo tablet daily.

06

What researchers measure

Primary outcomes

  1. Patient Global Rating of Pain for the Study Period (12 Weeks)

    3-item Likert-scale: "How do you rate overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective". The average of ratings at visits 2-5 was calculated as median, rounded up to the closest integer.

    Time frame: 12 weeks

  2. Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)

    Percentage of difference in WOMAC Pain Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.

    Time frame: Baseline to week 12

  3. Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)

    Percentage of difference in WOMAC Physical Function Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Physical Function subscale results from the sum of 17 questions.

    Time frame: Baseline to week 12

Secondary outcomes

  1. Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)

    Percentage of difference in WOMAC Pain Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.

    Time frame: Week 0, week 3, week 6

  2. Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)

    Percentage of difference in WOMAC Physical Function Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales. The WOMAC Physical Function Subscale comprises 17 questions each rated on a 100mm visual analog scale (VAS) ranging from no pain (0mm) to extreme pain (100mm).

    Time frame: Week 0, week 3, week 6

  3. Multiple Dose Effect Using 24-hour VAS Pain Questionnaire

    Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm).

    Time frame: 12 weeks

  4. Investigator Global Rating of Pain Relief

    The Investigator Global Rating of Pain is a 3-item Likert-scale to answer the following question: "How do you rate this patient's overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective".

    Time frame: 12 weeks

  5. Percentage of Participants Who Dropped Out From Trial by Dropout Reason

    Reasons for withdrawal from the trial were collected and the percentage of participants who dropped out from trial were calculated by dropout reason

    Time frame: 12 weeks

07

Results

Posted Aug 3, 2009

Participant flow

Participant flow — Overall Study
Milestone1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Started110113115227
Completed646054144
Not completed46536183
Withdrew: Lack of efficacy17151352
Withdrew: Withdrawal by subject57210
Withdrew: Physician decision212510
Withdrew: Administrative0001
Withdrew: Adverse event21194110
Withdrew: Death1000

Outcome measures

PrimaryPatient Global Rating of Pain for the Study Period (12 Weeks)

3-item Likert-scale: "How do you rate overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective". The average of ratings at visits 2-5 was calculated as median, rounded up to the closest integer.

Time frame:
12 weeks
Reported as:
Number · participants
Patient Global Rating of Pain for the Study Period (12 Weeks)
participants1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Very effective19162629
Effective50565694
Ineffective393731100
PrimaryPercentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)

Percentage of difference in WOMAC Pain Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.

Time frame:
Baseline to week 12
Reported as:
Mean · Percentage difference
Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)
Percentage difference1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Percentage Difference Between WOMAC Pain Subscale Score From Baseline to the End of the Study (Week 12)36.3 ± 45.336.6 ± 40.941.0 ± 44.538.0 ± 41.7
SecondaryPercentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)

Percentage of difference in WOMAC Pain Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Pain Subscale results from the sum of 5 questions.

Time frame:
Week 0, week 3, week 6
Reported as:
Mean · Percentage difference
Percentage Difference in WOMAC Pain Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Percentage difference1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Week 0 (Visit 2)26.7 ± 36.929.0 ± 33.433.1 ± 41.420.4 ± 35.8
Week 3 (Visit 3)35.2 ± 40.936.0 ± 40.342.3 ± 40.635.1 ± 39.4
Week 6 (Visit 4)36.3 ± 40.936.4 ± 39.547.7 ± 42.241.3 ± 39.9
SecondaryPercentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)

Percentage of difference in WOMAC Physical Function Subscale score between baseline and intervening visits 2-4. The WOMAC scale is a 24-item questionnaire divided in 3 subscales. The WOMAC Physical Function Subscale comprises 17 questions each rated on a 100mm visual analog scale (VAS) ranging from no pain (0mm) to extreme pain (100mm).

Time frame:
Week 0, week 3, week 6
Reported as:
Mean · Percentage difference
Percentage Difference in WOMAC Physical Function Subscale Score From Baseline to Intervening Visits (Visits 2-4)
Percentage difference1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Week 0 (Visit 2)23.4 ± 37.126.4 ± 30.929.3 ± 37.918.5 ± 37.7
Week 3 (Visit 3)33.3 ± 40.736.5 ± 34.441.0 ± 39.733.7 ± 38.2
Week 6 (Visit 4)33.5 ± 39.837.0 ± 36.847.7 ± 43.838.3 ± 37.8
SecondaryMultiple Dose Effect Using 24-hour VAS Pain Questionnaire

Patients rated their knee pain by marking a 100mm Visual Analogue Scale, ranging from no pain (0mm) to extreme pain (100mm).

Time frame:
12 weeks
Reported as:
Mean · mm
Multiple Dose Effect Using 24-hour VAS Pain Questionnaire
mm1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Pain at lunchtime (last individual visit)40.5 ± 29.938.2 ± 29.636.6 ± 29.438.5 ± 29.5
Pain at bed time (last individual visit)41.2 ± 30.741.1 ± 29.937.3 ± 30.239.7 ± 29.4
Pain Before next morning dose (last individ visit)41.1 ± 30.142.0 ± 29.535.5 ± 29.338.5 ± 29.8
SecondaryInvestigator Global Rating of Pain Relief

The Investigator Global Rating of Pain is a 3-item Likert-scale to answer the following question: "How do you rate this patient's overall pain relief with the drug?" with 3 possible answers: "very effective", "effective", or "ineffective".

Time frame:
12 weeks
Reported as:
Number · participants
Investigator Global Rating of Pain Relief
participants1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Very effective20142229
Effective49585798
Ineffective39373296
PrimaryPercentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)

Percentage of difference in WOMAC Physical Function Subscale score between baseline and week 12. The WOMAC scale is a 24-item questionnaire divided in 3 subscales, using a 100mm visual analog scale ranging from no pain (0mm) to extreme pain (100mm). The WOMAC Physical Function subscale results from the sum of 17 questions.

Time frame:
Baseline to week 12
Reported as:
Mean · Percentage difference
Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)
Percentage difference1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Percentage Difference Between WOMAC Physical Function Subscale Score From Baseline to the End of the Study (Week 12)31.9 ± 46.037.0 ± 39.337.3 ± 41.733.7 ± 44.3
SecondaryPercentage of Participants Who Dropped Out From Trial by Dropout Reason

Reasons for withdrawal from the trial were collected and the percentage of participants who dropped out from trial were calculated by dropout reason

Time frame:
12 weeks
Reported as:
Number · percentage of participants
Percentage of Participants Who Dropped Out From Trial by Dropout Reason
percentage of participants1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Lack of efficacy15.513.311.322.9
Patient request4.56.21.74.4
Investigator initiated discontinuation1.810.64.34.4
Administrative0000.4
Adverse event19.116.835.74.4
Death0.9000

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
1: Tramadol Once A Day 100mg—2/110 (1.8%)31/110 (28.2%)
2: Tramadol Once A Day 200mg—1/113 (0.9%)49/113 (43.4%)
3: Tramadol Once A Day 300mg—4/115 (3.5%)57/115 (49.6%)
4: Placebo—3/227 (1.3%)38/227 (16.7%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
Event1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
Bipolar disorder NECPsychiatric disorders1/1100/1130/1150/227
Deep venous thrombosis NOSVascular disorders1/1100/1130/1150/227
Acute myocardial infarctionCardiac disorders1/1100/1130/1150/227
Breast cancer invasive NOSNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1101/1130/1150/227
Aortic aneurysmVascular disorders0/1100/1131/1150/227
Pancreatitis aggravatedGastrointestinal disorders0/1100/1131/1150/227
Thyroid neoplasm NOSNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1100/1131/1150/227
Faecal impactionGastrointestinal disorders0/1100/1131/1150/227
Gastroenteritis viral NOSGastrointestinal disorders0/1100/1130/1151/227
Rectal prolapseGastrointestinal disorders0/1100/1130/1151/227
Most frequent other events
Most frequent other events
Event1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: Placebo
NauseaNervous system disorders17/11025/11332/11514/227
DizzinessNervous system disorders7/11020/11325/1155/227
ConstipationGastrointestinal disorders10/11017/11318/11515/227
VomitingGastrointestinal disorders4/1108/11314/1152/227
HeadacheNervous system disorders7/1106/11310/11515/227

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: PlaceboTotal
<=18 years00000.0
Between 18 and 65 years697766139351.0
>=65 years41364988214.0
Age Continuous
Age Continuous(years)1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: PlaceboTotal
Mean59.8 ± 9.059.8 ± 8.461.0 ± 9.660.6 ± 9.660.4 ± 9.3
Sex: Female, Male
Sex: Female, Male(Participants)1: Tramadol Once A Day 100mg2: Tramadol Once A Day 200mg3: Tramadol Once A Day 300mg4: PlaceboTotal
Female656472140341.0
Male45494387224.0
08

Study locations

No study locations are listed for this record.

09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 30, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00832416
Lead sponsor
Labopharm Inc.
Responsible party
Sponsor
First posted
Jan 30, 2009
Start date
Jan 2003
Primary completion
Aug 2003
Results posted
Aug 3, 2009
Last update
Apr 30, 2012
View the source record on ClinicalTrials.gov ↗

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