Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy

Study Overview
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Brief Summary
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The study evaluates the effectiveness and safety of IV tramadol compared to placebo managing postoperative pain following a bunionectomy

Detailed Description
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(Non-clinical summary) Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with opioidlike effects. Tramadol is extensively metabolized following administration, which results in a number of enantiomeric metabolites that display different opioid-receptor binding properties, and monoaminergic reuptake inhibition.

Official Title
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A Phase 3, Multicenter, Randomized, Double Blind, Three-Arm Study to Evaluate the Efficacy and Safety of Tramadol Infusion (AVE-901) Versus Placebo in the Management of Postoperative Pain Following Bunionectomy

Conditions
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Pain Management

Intervention / Treatment
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* Drug: Tramadol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The patient is male or female 18-75 years of age undergoing unilateral first metatarsal bunionectomy surgery Willing to give consent and able to understand the study procedures Female patients must be of non-childbearing potential or be practicing a highly effective contraception The patient must be willing to be housed in a healthcare facility and able to receive parenteral analgesia for at least 72 hours after surgery. The patient meets definition of American Society of Anesthesiologists (ASA) Physical Class 1, or 2. Exclusion Criteria: Patient is not expected to receive a continuous infusion nerve block as described in the Post-Op anesthetic procedures protocol Patient is undergoing bilateral or revision bunionectomy surgery The patient has allergy or hypersensitivity (or is intolerant) to opioids or tramadol The patient has known physical dependence on opioids The patient has taken other prior/concurrent chronic medications that have not been at a stable dose for at least 2 weeks prior to screening The patient is taking herbal or dietary supplements or medications that are moderate or strong inhibitors of CYP2D6 or CYP3A4 or inducers of CYP3A4 The patient has taken monoamine oxidase (MAO) inhibitors, trazodone, or cyclobenzaprine within 14 days prior to surgery The patient cannot be withdrawn from medications (at least 7 days prior to surgery) that may lower the seizure threshold (e.g. anti-psychotic agents, MAOI inhibitors) or which increase serotonergic tone (e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, triptans). The patient has a history of epilepsy, or is known to be susceptible to seizures The patient has a history of Long QT Syndrome or a relative with this condition The patient has expressed suicidal ideation or is considered to be at risk of suicide. The patient is morbidly obese (body mass index [BMI] ≥ 40 kg/m2) or has documented sleep apnea requiring pharmacological or device intervention. Clinically significant abnormalities in the judgement of the Investigator The patient was administered an investigational product within 30 days prior to Screening. The patient has previously participated in a clinical study with AVE-901.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AVE-901 50 mg<br> | Drug: Tramadol<br>* IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44<br>|
| Active Comparator: AVE-901 25 mg<br> | Drug: Tramadol<br>* IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose | Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity. | 48 hours post first dose |