A Study to Evaluate the Effectiveness and Safety of Tapentadol (CG5503) in the Treatment of Acute Pain From Bunionectomy Compared With Placebo

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Tapentadol Immediate-Release Formulation in the Treatment of Acute Pain From Bunionectomy

The purpose of this study is to evaluate the analgesic efficacy and safety of tapentadol immediate-release (IR [CG5503]) for use in the relief of moderate to severe acute pain, compared with placebo, in adult Taiwanese patients with acute pain following bunionectomy.

Patients undergoing bunionectomy (a surgical procedure to remove a bunion, an enlargement of the joint at the base of the big toe comprised of bone and soft tissue) often experience moderate to severe acute pain post-surgery. Normally such pain is controlled when patients receive repeated doses of opioid analgesics. Tapentadol (CG5503) is a newly synthesized opioid drug acting as a centrally acting analgesic like opioid analgesics but has a different mode of action. This study, a randomized (patients are assigned different treatments based on chance), double-blind (neither investigator nor patient knows which treatment the patient receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each group of patients will be treated at the same time), multicenter study (the study is performed at more than one clinic) is designed to evaluate the effectiveness (level of pain control) and safety (side effects) of tapentadol immediate-release (IR) 50 mg or 75 mg versus placebo. The study will consist of a screening phase, during which the patients will be evaluated for study entry (Days -28 to -2) followed by the surgical period (Day -1) during which the bunionectomy will be performed and which will start with the first surgical incision and continues until termination of the popliteal sciatic block (PSB) infusion. During the qualification period (Day 1) which starts after termination of the post-operative continuous PSB infusion, patients will be evaluated for entry in the double blind treatment phase. Patients will be randomly assigned to one of three treatment groups to receive either 50 mg tapentadol IR, 75 mg tapentadol IR or a placebo if their PI is equal to or greater than 4 on a 0-10 numerical rating scale. The inpatient double-blind treatment period will be 72 hours in duration and will include a final end-of-double-blind evaluation (on Day 4, i.e., 72 hours after the administration of the first dose) for all patients. Any patient requiring analgesia for pain relief in addition to study drug during the double-blind treatment period will be discontinued from the study due to lack of efficacy. All patients who discontinue for lack of efficacy will complete pain assessments and the Patient Global Impression of Change (PGIC) before receiving rescue medication. Pain intensity and pain relief will be periodically assessed during the treatment period using rating scales. Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. The study length, including the screening period, will be up to a maximum duration of 32 days.

Inclusion Criteria:

• Patients must be undergoing primary unilateral first metatarsal bunionectomy that includes a distal Chevron osteotomy only, with or without the Akin procedure
• Patients must be healthy or medically stable on the basis of clinical laboratory tests performed at screening
• Women must be postmenopausal, surgically sterile, abstinent, or practicing or agree to practice an effective method of birth control and have a negative serum pregnancy test at screening and a negative urine pregnancy test before surgery
• If a male, must use an approved method of birth control and does not donate sperm from the day of study drug administration until 3 months afterwards
• Qualifying baseline Pain Intensity must be rated as greater than or equal to 4 on an 11-point (0 to 10) PI NRS, recorded within 30 minutes before randomization, no earlier than 10 hours after the first surgical incision and within 9 hours after termination of the continuous Popliteal Sciatic Block (PSB) infusion Exclusion Criteria: - History of seizure disorder or epilepsy, severe traumatic brain injury, episode(s) of unconsciousness of more than 24 hours duration, malignancy in the past 2 years with the exception of successfully treated basal cell carcinoma
• Mild or moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1 year of screening
• Renal insufficiency, impaired hepatic function
• Use of anticonvulsants, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), neuroleptics, serotonin norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs) or triptans