Acute Low Back Pain
Conditions
Keywords
Back Pain
Brief summary
The primary objective of this study is to determine the time of onset of analgesic effect of Tramadol Contramid® Once-A-Day (OAD) in acute low back pain. Secondary objectives include determining the relationship between analgesic effect and plasma levels for Tramadol Contramid® OAD and to examine safety after single dose administration of 200 mg of Tramadol Contramid® OAD.
Interventions
DRUGTramadol Contramid® OAD 200mg
1 Tramadol Contramid® OAD 200mg tablet daily.
Sponsors
Labopharm Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males or females in generally good health aged 18-80 years with acute low back pain are eligible for this study. * Patients must have pain of moderate to severe intensity on the patient rating of pain intensity scale without analgesia. * Oral and written language comprehension at a level sufficient to comply with the protocol and complete study-related materials. * Must have signed and dated an REB-approved written Informed Consent form which was also signed and dated by the Investigator prior to study participation.
Exclusion criteria
* Known history or symptoms suspicious of: * Spinal fracture * Cancer (i.e. constitutional symptoms such as recent unexplained chills or weight loss) * Spinal infection (e.g. IV drug abuse, immunosuppression) * Cauda equina syndrome * Spina bifida * Foot drop * Spinal surgery within 1 year of study entry * Body Mass Index (BMI) \> 37 * Continuous chronic back pain * More severe pain in a region other than the lower back * Treatment of the back pain with non-pharmacological therapy (e.g. acupuncture chiropractic adjustment, Transcutaneous Electrical Nerve Stimulation, physiotherapy etc.) in the 3 weeks prior to study entry * Use of any sedative hypnotics, topical preparations/medications and anaesthetics or muscle relaxants within 5 half-lives of the dose of study medication * Use of any analgesic within 6 hours of the dose of study medication. In rare cases, if a patient is in moderate to severe pain despite having taken a short-acting analgesic and if at least 2 hours have passed since the dose of short-acting analgesic, the patient may be entered. * A major illness, requiring hospitalisation during the 3 months before commencement of the screening period * Unwillingness to stop taking pain medication other than the study medication * Previous failure of treatment with tramadol or discontinuation of treatment with tramadol due to adverse events * 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 (SSRIs); serotonin-norepinephrine reuptake inhibitors (SNRIs) or any other drug that reduces seizure threshold * Treatment with another investigational agent within the last 30 days * History of seizure disorder other than Infantile Febrile Seizures * Previous or current opioid dependency * Bowel disease causing malabsorption * Pregnant or lactating women * Known significant liver disease or symptoms of significant liver disease * Known significant renal disease or symptoms of significant renal disease * Current or past substance abuse or dependence, other than nicotine * Allergy to tramadol or any structurally similar drugs (e.g. opiates) * Any other condition that, in the opinion of the Investigators, would adversely affect the patient's ability to complete the study or its measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Perceptible Pain Relief | 6 hours | Kaplan-Meier estimates of time to perceptible pain relief. Patients who discontinued or completed the study without perceptible pain relief were censored at the time point of their last pain intensity score. A confidence interval for the median survival time was calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Baseline, 3 hours post-dose, 6 hours post-dose, time of onset of perceptible pain relief | Pain intensity rating at baseline, time of onset of perceptible pain relief, 3 hours and 6 hours post-dose or if the patient discontinued earlier. What is your current level of pain intensity? 0=none, 1=mild, 2=moderate, 3=severe. Missing data were imputed using Last Observation Carried Forward (LOCF). |
| Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, 6 hours post-dose, at time of onset of perceptible pain relief | Pain relief rating at time of onset of perceptible pain relief, 3 hours and 6 hours post-dose or if the patient discontinued earlier. How would you rate the pain relief the study medication has given you? ranging from 0=none to 4=complete relief. Missing data were imputed using Last Observation Carried Forward (LOCF). |
| Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose | Baseline, time of onset of perceptible pain relief, 3 hours post-dose, 6 hours post-dose | PK samples were drawn at the end of the Screening Phase, at the onset of perceptible pain relief, at 3 hours and at 6 hours post-dose or if the patient discontinues early. PK samples were always drawn after the completion of the patient ratings of pain relief and of pain intensity scales. They were processed in a central laboratory and the plasma levels of tramadol were collected. |
| Number of Participants With Adverse Events | 6 hours | All adverse events reported during treatment with study drug were considered and reported as treatment emergent adverse events (TEAE) whether or not medication for this adverse event was required by the participant and were summarized in the same table. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tramadol Contramid® Once-A-Day (OAD) Single dose 200 mg of Tramadol Contramid® Once-A-Day (OAD) | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Tramadol Contramid® Once-A-Day (OAD) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age Continuous | 61.2 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment Romania | 47 participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 47 |
| serious Total, serious adverse events | 0 / 47 |
Outcome results
Primary
Time to Onset of Perceptible Pain Relief
Kaplan-Meier estimates of time to perceptible pain relief. Patients who discontinued or completed the study without perceptible pain relief were censored at the time point of their last pain intensity score. A confidence interval for the median survival time was calculated.
Time frame: 6 hours
Population: Full analysis population: includes all patients who received the dose of study medication and who had at least one pharmacodynamic assessment during the dosing phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tramadol Contramid® Once-A-Day (OAD) | Time to Onset of Perceptible Pain Relief | 47 minutes |
Secondary
Number of Participants With Adverse Events
All adverse events reported during treatment with study drug were considered and reported as treatment emergent adverse events (TEAE) whether or not medication for this adverse event was required by the participant and were summarized in the same table.
Time frame: 6 hours
Population: Safety population: includes all patients who received the dose of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tramadol Contramid® Once-A-Day (OAD) | Number of Participants With Adverse Events | Patients with at least one TEAE requiring therapy | 3 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Number of Participants With Adverse Events | Patients with at least one TEAE | 23 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Number of Participants With Adverse Events | Patients with at least one severe TEAE | 5 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Number of Participants With Adverse Events | Patients with at least 1 possibly drug related AE | 23 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Number of Participants With Adverse Events | Patients with at least one SAE | 0 participants |
Secondary
Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose
Pain intensity rating at baseline, time of onset of perceptible pain relief, 3 hours and 6 hours post-dose or if the patient discontinued earlier. What is your current level of pain intensity? 0=none, 1=mild, 2=moderate, 3=severe. Missing data were imputed using Last Observation Carried Forward (LOCF).
Time frame: Baseline, 3 hours post-dose, 6 hours post-dose, time of onset of perceptible pain relief
Population: Full analysis population: includes all patients who received the dose of study medication and who had at least one pharmacodynamic assessment during the dosing phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Baseline, moderate pain | 34 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Baseline, severe pain | 12 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, mild pain | 23 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, moderate pain | 19 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, no pain | 12 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, mild pain | 25 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, mild pain | 20 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, moderate pain | 2 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, no pain | 4 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, moderate pain | 9 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Intensity at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, no pain | 24 participants |
Secondary
Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose
Pain relief rating at time of onset of perceptible pain relief, 3 hours and 6 hours post-dose or if the patient discontinued earlier. How would you rate the pain relief the study medication has given you? ranging from 0=none to 4=complete relief. Missing data were imputed using Last Observation Carried Forward (LOCF).
Time frame: 3 hours post-dose, 6 hours post-dose, at time of onset of perceptible pain relief
Population: Full analysis population: includes all patients who received the dose of study medication and who had at least one pharmacodynamic assessment during the dosing phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, no pain relief | 1 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, a little relief | 16 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, complete relief | 4 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, no pain relief | 2 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, a little relief | 3 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, moderate relief | 9 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | Onset of perceptible pain relief, a lot of relief | 16 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, moderate relief | 12 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, a lot of relief | 17 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 3 hours post-dose, complete relief | 12 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, no pain relief | 1 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, a little relief | 2 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, moderate relief | 1 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, a lot of relief | 18 participants |
| Tramadol Contramid® Once-A-Day (OAD) | Patient Rating of Pain Relief at Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post Dose | 6 hours post-dose, complete relief | 24 participants |
Secondary
Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose
PK samples were drawn at the end of the Screening Phase, at the onset of perceptible pain relief, at 3 hours and at 6 hours post-dose or if the patient discontinues early. PK samples were always drawn after the completion of the patient ratings of pain relief and of pain intensity scales. They were processed in a central laboratory and the plasma levels of tramadol were collected.
Time frame: Baseline, time of onset of perceptible pain relief, 3 hours post-dose, 6 hours post-dose
Population: Full analysis population: includes all patients who received the dose of study medication and who had at least one pharmacodynamic assessment during the dosing phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tramadol Contramid® Once-A-Day (OAD) | Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose | 0 hour | 5.17 ng/ml | Standard Deviation 1.55 |
| Tramadol Contramid® Once-A-Day (OAD) | Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose | 3 hours post-dose | 176.34 ng/ml | Standard Deviation 48.68 |
| Tramadol Contramid® Once-A-Day (OAD) | Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose | Onset of perceptible pain relief | 56.10 ng/ml | Standard Deviation 37.61 |
| Tramadol Contramid® Once-A-Day (OAD) | Plasma Levels of Tramadol at 0 Hour (Baseline), Onset of Perceptible Pain Relief, 3 Hours and 6 Hours Post-dose | 6 hours post-dose | 187.98 ng/ml | Standard Deviation 67.03 |