Study to Evaluate the Analgesic Efficacy and Safety of Hydrocodone Bitartrate/Acetaminophen Immediate-Release Tablets in Participants With Moderate to Severe Pain Following Bunionectomy
Condition: Pain
Intervention: TV-46763; Placebo
Intervention description: TV-46763 will be administered per dose and schedule specified in the arm description.; Placebo matching to TV-46763 will be administered per schedule specified in the arm description.
Intervention MeSH terms: Acetaminophen; Acetaminophen, hydrocodone drug combination; Hydrocodone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 569.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the analgesic efficacy of hydrocodone
      bitartrate/acetaminophen immediate-release tablets at doses of 5.0 milligrams (mg)/325 mg,
      7.5 mg/325 mg, and 10 mg/325 mg every 4 to 6 hours compared with placebo in treating
      participants with moderate to severe pain following bunionectomy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women aged 18 to 75 years, inclusive.

          2. Participants who are scheduled to undergo a primary unilateral first metatarsal Austin
             bunionectomy with distal osteotomy and internal fixation without any collateral
             procedures (ie, uncomplicated procedure).

          3. Participants who according to the American Society of Anesthesiologists Physical
             Status (PS) classification system are classified PS-1 (normal, healthy participant) or
             PS-2 (mild systemic disease).

          4. The participant is able to speak English and is willing to provide written informed
             consent, including a written opioid agreement, to participate in the study.

          5. The participant has a body mass index (BMI) between 18.0 and 33.0 kg/m2 (inclusive) at
             the time of screening.

          6. The participant is in generally good health as determined by a medical history,
             medical examination, ECG, serum chemistry, hematology, urinalysis, and serology.

          7. Women of childbearing potential (not surgically sterile or 2 years postmenopausal)
             must use a medically acceptable method of contraception and must agree to continue use
             of this method for the duration of the study and for 30 days after discontinuation of
             the study drug, unless they have exclusively same-sex partners. Acceptable methods of
             contraception include intrauterine device (IUD) known to have a failure rate of less
             than 1% per year, hormonal contraceptive (oral, implanted, transdermal, or injected),
             and barrier method with spermicide, abstinence, and partner vasectomy.

             NOTE: A woman will be considered surgically sterile if she has had a tubal ligation,
             hysterectomy, bilateral salpingo-oophorectomy or bilateral oophorectomy, or
             hysterectomy with bilateral salpingo-oophorectomy.

          8. The participant, if a man, is surgically sterile, or, if capable of producing
             offspring, is currently using a medically acceptable method of contraception and
             agrees to continue use of this method for the duration of the study (and for 90 days
             after taking the last dose of the study drug because of the possible effects on
             spermatogenesis), unless he has exclusively same-sex partners. Acceptable methods of
             contraception include abstinence, barrier method with spermicide, female partner's use
             of steroidal hormonal contraceptive (oral, implanted, transdermal, or injected) in
             conjunction with a barrier method, female partner's use of an IUD known to have a
             failure rate of less than 1% per year, or if his female partner is surgically sterile
             or 2 years postmenopausal. In addition, male participants may not donate sperm for the
             duration of the study and for 90 days after taking study drug.

          9. The participant must be willing and able to comply with study restrictions and to
             remain at the clinic for the required duration during the study, and willing to return
             to the clinic for the follow-up evaluation as specified in this protocol.

         10. The participant must not participate in any other study involving an investigational
             agent while enrolled in the present study.

         11. The participant must report a pain intensity score of ≥4 on an 11-point NPRS-11 within
             9 hours after stopping postsurgical analgesia and immediately before randomization.

         12. The participant should be free of any surgical or anesthetic complications after the
             surgery, which is to be performed using the intraoperative anesthetic regimen and the
             postoperative analgesic regimen that was followed appropriately without deviations
             that would confound analgesic assessments after receipt of the investigational
             product.

        Exclusion Criteria:

          1. The participant has a chronic pain condition, excluding bunion pain that requires
             taking opioid analgesics within 30 days prior to surgery or use of non-opioid
             analgesics (acetylsalicylic acid, acetaminophen, nonsteroidal anti-inflammatory drugs)
             within 24 hours prior to surgery. Stable therapy of >30 days for acetylsalicylic acid
             (up to 81 mg/day) is allowed as cardiovascular prophylaxis.

          2. Use of glucocorticoids (except nasal corticosteroid sprays and/or topical
             corticosteroids) for any condition within 6 months before study drug administration.

          3. The participant uses any nonpharmacologic pain management techniques (eg, physical
             techniques, physiotherapy, massage therapy, acupuncture, biofeedback, and/or
             psychological support) and is unable or unwilling to discontinue prior to
             randomization (or study start).

          4. The participant has any other medical or psychiatric condition or is receiving
             concomitant medication/therapy that would, in the opinion of the investigator,
             compromise the participant's safety, compliance with the study protocol procedures, or
             collection of data.

          5. The participant has a clinically significant abnormality in the physical examination
             and/or clinical laboratory test values.

          6. The participant is a pregnant or lactating woman. (Any woman becoming pregnant during
             the study will be withdrawn from the study.)

          7. The participant has used an investigational drug within 1 month before the screening
             visit.

          8. The participant is participating any currently ongoing research study.

          9. The participant has any disorder that may interfere with gastrointestinal (GI) drug
             absorption (eg, gastric bypass surgery, lap band, malabsorption syndrome, and
             inflammatory bowel disease) or other condition that may have an effect on participant
             safety or efficacy aspects of participation in the opinion of the investigator.

         10. The participant is allergic to or has had a serious reaction to hydrocodone or other
             opioids, acetaminophen, ropivacaine, lidocaine, ketorolac, ibuprofen, propofol, or any
             of the drugs required by the study protocol.

         11. The participant has a recent history (within 5 years) or current evidence of alcohol
             or other substance abuse, with the exception of nicotine.

         12. The participant has a positive urine drug screen (UDS) for cocaine, marijuana,
             opioids, amphetamines, methamphetamines, benzodiazepines, barbiturates, and/or
             methadone, unless explained by the use of prescription medication.

         13. The participant has a history of suicidality as assessed by participant medical
             history and/or the C-SSRS.

         14. The participant is expected to have elective surgery during the study other than a
             bunionectomy.

         15. The participant has a history of malignancy within 5 years (except for treated basal
             cell carcinoma).

         16. The participant has a positive test result for hepatitis B surface antigen or
             antibodies to hepatitis C, or known or tested positive for human immunodeficiency
             virus.

         17. The participant has received a monoamine oxidase inhibitor (MAOI) within 14 days
             before the first dose of study drug.

         18. The investigator believes that the participant is not suitable for the study for any
             reason.