Maxigesic IV Phase 3 Bunionectomy Study
Condition: Post Operative Pain
MeSH terms: Pain, Postoperative
Intervention: Maxigesic IV; IV Acetaminophen; IV Ibuprofen; Placebo IV
Intervention description: IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours; IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours; IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours; Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
Intervention MeSH terms: Acetaminophen; Ibuprofen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 276.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Analgesic

Summary:

      The purpose of the study is to determine the clinical efficacy and safety of Maxigesic IV,
      acetaminophen IV, Ibuprofen IV versus placebo IV for the treatment of acute postoperative
      pain after bunionectomy
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is male or female ≥ 18 and ≤ 65 years of age.

          2. Is classified by the anesthesiologist as P1 to P2 in the American Society of
             Anesthesiologists (ASA) Physical Status Classification System.

          3. Has undergone primary, unilateral, distal, first metatarsal bunionectomy (osteotomy
             and internal fixation) with no additional collateral procedures.

          4. Experiences a pain intensity rating of ≥ 40 mm on a 100-mm Visual Analogue Scale (VAS)
             during the 9-hour period after discontinuation of the anesthetic block.

          5. Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 40 kg/m2.

          6. If female and of childbearing potential, is nonlactating and nonpregnant (has negative
             pregnancy test results at Screening [urine] and on the day of surgery prior to surgery
             [urine]).

          7. If female, is 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 medically acceptable methods of
             birth control:

             Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives
             for a minimum of 1 full cycle (based on the subject's usual menstrual cycle period)
             before study drug administration.

             Total abstinence from sexual intercourse since the last menses before study drug
             administration through completion of final study visit.

             Intrauterine device (IUD). Double-barrier method (condoms, sponge, diaphragm, or
             vaginal ring with spermicidal jellies or cream).

          8. Is able to provide written informed consent to participate in the study and able to
             understand the procedures and study requirements.

          9. Must voluntarily sign and date an informed consent form (ICF) that is approved by an
             Institutional Review Board (IRB) before the conduct of any study procedure.

         10. Is willing and able to comply with study requirements (including diet, alcohol, and
             smoking restrictions), complete the pain evaluations, remain at the study site for
             approximately 72 hours, and return for follow-up 7 ± 2 days after surgery.

        Exclusion Criteria:

          1. Has a known history of allergic reaction or clinically significant intolerance to
             acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs,
             including ibuprofen); history of NSAID-induced bronchospasm (subjects with the triad
             of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and
             should be considered carefully); or hypersensitivity, allergy, or significant reaction
             to sulfa (including sulfonamide) medicines, ingredients of the study drug, or any
             other drugs used in the study including anesthetics and antibiotics that may be
             required on the day of surgery.

          2. Has experienced any surgical complications or other issues that, in the opinion of the
             investigator, could compromise the safety of the subject if he or she continues into
             randomized treatment period or could confound the results of the study.

          3. Has known or suspected history of alcoholism or drug abuse or misuse within 2 years of
             screening or evidence of tolerance or physical dependence before dosing with study
             drug.

          4. Has any clinically significant unstable cardiac, respiratory, neurological,
             immunological, hematological, or renal disease or any other condition that, in the
             opinion of the investigator, could compromise the subject's welfare, ability to
             communicate with the study staff, or otherwise contraindicate study participation.

          5. Has any ongoing condition, other than a condition associated with the current primary,
             unilateral, first metatarsal bunionectomy that could generate levels of pain
             sufficient to confound the results of the study (eg, gout, severe osteoarthritis of
             the target joint or extremity).

          6. Has a history or current diagnosis of a significant psychiatric disorder that, in the
             opinion of the investigator, would affect the subject's ability to comply with the
             study requirements.

          7. Has tested positive either on the urine drug screen or on the alcohol breathalyzer
             test. Subjects who test positive at Screening only and can produce a prescription for
             the medication from their physician may be considered for study enrolment at the
             discretion of the investigator.

          8. Has a history of a clinically significant (investigator opinion) gastrointestinal (GI)
             event within 6 months before Screening or has any history of peptic or gastric ulcers
             or GI bleeding.

          9. Has a surgical or medical condition of the GI or renal system that might significantly
             alter the absorption, distribution, or excretion of any drug substance.

         10. Is considered by the investigator, for any reason (including, but not limited to, the
             risks described as precautions, warnings, and contraindications in the current version
             of the Investigator's Brochure for IV Maxigesic®), to be an unsuitable candidate to
             receive the study drug.

         11. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been
             diagnosed with cancer within 5 years before Screening (excluding treated squamous or
             basal cell carcinoma of the skin).

         12. Is currently receiving anticoagulants (eg, heparin or warfarin).

         13. Has received a course of systemic corticosteroids (either oral or parenteral) within 3
             months before Screening (inhaled nasal steroids and regional/limited area application
             of topical corticosteroids (investigator discretion) are allowed).

         14. Has received or will require any analgesic medication within 5 half-lives (or, if
             half-life is unknown, within 48 hours) before surgery.

         15. Has a history of chronic use (defined as daily use for > 2 weeks) of NSAIDs, opiates,
             or glucocorticoids (except inhaled nasal steroids and regional/limited topical
             corticosteroids), for any condition within 6 months before study drug administration.
             Aspirin at a daily dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the
             subject has been on a stable dose regimen for ≥ 30 days before Screening and has not
             experienced any relevant medical problem.

         16. Has been treated with agents that could affect the analgesic response (such as central
             alpha agents [clonidine and tizanidine], neuroleptic agents, and other antipsychotic
             agents) within 2 weeks before dosing with study drug.

         17. Has a significant renal or hepatic disease, as indicated by clinical laboratory
             assessment (results ≥ 3 times the upper limit of normal [ULN] for any liver function
             test, including aspartate aminotransferase [AST], alanine aminotransferase [ALT], and
             lactate dehydrogenase, or creatinine ≥ 1.5 times the ULN).

         18. Has any clinically significant laboratory finding at Screening that, in the opinion of
             the investigator, contraindicates study participation.

         19. Has significant difficulties swallowing capsules or is unable to tolerate oral
             medication.

         20. Previously participated in another clinical study of Maxigesic® IV or received any
             investigational drug or device or investigational therapy within 30 days before
             Screening.