A Pharmacodynamic/Pharmacokinetic Study to Determine the Onset of Analgesic Effect and Plasma Levels of Tramadol in Patients With Acute Low Back Pain Receiving a Single 200 mg Dose of Tramadol Contramid® Once-a-Day

Study Overview
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Brief Summary
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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.

Official Title
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A Pharmacodynamic/Pharmacokinetic Study to Determine the Onset of Analgesic Effect and Plasma Levels of Tramadol in Patients With Acute Low Back Pain Receiving a Single 200 mg Dose of Tramadol Contramid® Once-a-Day

Conditions
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Acute Low Back Pain

Intervention / Treatment
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* Drug: Tramadol Contramid® OAD 200mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol Contramid® OAD 200mg<br>1 Tramadol Contramid® OAD 200mg tablet daily. | Drug: Tramadol Contramid® OAD 200mg<br>* 1 Tramadol Contramid® OAD 200mg tablet daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, 3 hours post-dose, 6 hours post-dose, time of onset of perceptible pain relief | 
| 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). | 3 hours post-dose, 6 hours post-dose, at time of onset of perceptible pain relief | 
| 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. | Baseline, time of onset of perceptible pain relief, 3 hours post-dose, 6 hours post-dose | 
| 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. | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Back Pain