Co-crystal E-58425 vs Tramadol and Celecoxib for Moderate to Severe Acute Pain After Bunionectomy. Phase III Clinical Trial.

Inclusion Criteria

• Subject must have signed consent before study entry.
• Subject must be at least 18 years old, scheduled to undergo primary unilateral first metatarsal osteotomy with internal fixation with no additional collateral procedure.
• Male and female subjects are eligible. If female, subject must be either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or practicing 1 of the following effective methods of birth control:
• Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives.
• Total abstinence from sexual intercourse since the last menses before study medication administration.
• Intrauterine device
• Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream).

Women must use effective methods of birth control from 6 weeks before administration of study medication until 4 weeks after the last administration.

• If female and of childbearing potential, subject must be non-lactating and non pregnant (has negative serum pregnancy test results at Screening and negative urine test on the day of surgery prior to surgery).
• Subject must have a body weight of 45 kg or more and a body mass index (BMI) of 40 kg/m2 or less.
• Subject must have a qualifying pain score of ≥5 and 9 on a 0-10 NPRS.
• Subject received any analgesic medication other than short-acting pre-operative or intra-operative anesthetic agents before the end of bunionectomy surgical procedure. Subjects who received any analgesic medication immediately after the bunionectomy surgical procedure was completed and before study medication is administered will also be excluded, with the exception of ketorolac 30 mg intravenously supplemental analgesia during the continuous infusion period and up until 1:00 A.M.
• Subject has a history of seizures or alcohol abuse (eg, drinks >4 units of alcohol per day, a unit being equal to 8 oz. beer, 3 oz. wine, 1 oz. spirits) within the past 5 years, has a history of prescription/illicit drug abuse within 6 months before dosing with study medication, or has positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse.
• Subject has a history of or positive test results for human immunodeficiency virus or hepatitis B or C.
• Subject has an active malignancy of any type, or has been diagnosed with cancer within 5 years before Screening (excluding successfully treated squamous or basal cell carcinoma of the skin).
• Subject is currently receiving anticoagulants (eg, heparin or warfarin) or antiplatelets (except aspirin ≤325 mg/day).
• Subject has received a course of systemic (either oral or parenteral) or intra-articular corticosteroids within 3 months before Screening (inhaled nasal steroids and topical corticosteroids are allowed).
• Subject has any ongoing condition, other than one associated with the current primary, unilateral, first metatarsal bunionectomy, that, in the investigator's opinion, could generate levels of pain sufficient to confound assessments of post-operative pain (eg, severe osteoarthritis of the target joint or extremity, fibromyalgia, rheumatoid arthritis, moderate to severe headache, diabetic foot pain or neuropathy).
• Subject has been receiving or has received chronic (defined as daily use for >2 weeks) opioid (oral codeine, dextromoramide, dihydrocodeine, oxycodone, or morphine-like anti-tussive) therapy defined as >15 morphine equivalents units per day for more than 3 out of 7 days per week over a 1-month period within 12 months of surgery, or has been treated chronically with opioid analgesic (buprenorphine, nalbuphine, or pentazocine) or NSAIDs within 30 days before Screening.
• Subject received a long-acting Non-Steroidal Anti-Inflammatory Drug (NSAID) within 4 days before initiation of study medication (except aspirin ≤325 mg/day), or