Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy

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

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

(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.

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• The patient cannot be withdrawn from medications (at least 7 days prior to surgery) that may lower the seizure threshold (e.g. anti-psychotic agents, MAOI inhibitors) or which increase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.