Study of Buprenorphine Sublingual Spray Versus Standard of Care Narcotic Therapy for the Treatment of Post-Operative Pain
Condition: Pain, Postoperative
MeSH terms: Pain, Postoperative
Intervention: Buprenorphine Sublingual Spray; Morphine; Oxycodone Hydrochloride; Zofran
Intervention description: 0.5 mg Sublingual Spray; 4 mg Intravenous Injection; 10 mg tablet; 4 mg oral disintegrating tablet (ODT) or IV injection given at the investigator's discretion for nausea
Intervention MeSH terms: Morphine; Oxycodone; Buprenorphine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study will evaluate the safety and tolerability based on the incidence of adverse
      experiences of buprenorphine sublingual spray (0.5 milligrams [mg] three times daily [TID])
      compared with standard post-operative narcotic therapy in participants with postoperative
      pain. Standard post-operative narcotic therapy is defined as morphine intravenous (IV)
      injection (4 mg TID) followed by oxycodone hydrochloride tablet (10 mg TID).
    

Eligibility criteria:

        Inclusion criteria:

          1. Is able to speak and understand the language in which the study is being conducted, is
             able to understand and comply with the procedures and study requirements, and has
             voluntarily signed and dated an informed consent form approved by an Institutional
             Review Board before the conduct of any study procedure.

          2. Is a male or female ≥18 and ≤65 years of age.

          3. Scheduled for elective bunionectomy, breast augmentation (in women only), or
             abdominoplasty.

          4. Is classified using the American Society of Anesthesiologists Physical Status
             Classification System as P1 to P2.

          5. 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 one of the following medically acceptable methods of
             birth control:

               1. Hormonal methods such as oral, implantable, injectable, vaginal ring, or
                  transdermal contraceptives for a minimum of 1 full cycle (based on the
                  participant's usual menstrual cycle period) before study drug administration;

               2. Total abstinence from sexual intercourse since the last menses before study drug
                  administration;

               3. Intrauterine device; OR

               4. Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or
                  cream).

          6. Has a body weight ≥45 kilograms (kg) and a body mass index (BMI) ≤40 kg/m^2.

          7. Is willing and able to comply with study requirements (including diet, alcohol, and
             smoking restrictions), complete evaluations and diary, remain at the study site for
             ≥72 hours, and return for follow up Day 8 + 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);
             history of NSAID-induced bronchospasm (participants 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 investigator's
             opinion, could compromise the participant's safety if he or she continues into
             randomized treatment or could confound the results of the study.

          3. Has a known or suspected history of alcoholism or drug abuse or misuse within 2 years
             of Screening or evidence of opioid tolerance or physical dependence before dosing with
             the study drug.

          4. Has any clinically significant unstable cardiac, respiratory, neurological,
             immunological, hematological, or renal disease, or any other condition that, in the
             investigator's opinion, could compromise the participant's welfare, ability to
             communicate with the study staff, or otherwise contraindicate study participation.

          5. Has long QT Syndrome, a family history of long QT Syndrome, or is taking Class IA or
             Class III antiarrhythmic medications

          6. Has a history or current diagnosis of a significant psychiatric disorder that, in the
             investigator's opinion, would affect the participant's ability to comply with the
             study requirements.

          7. Has tested positive either on the urine drug screen or on the alcohol Breathalyzer
             test. Participants who test positive at Screening only and can produce a prescription
             in their name from their physician for the medication producing the positive test may
             be considered for study enrollment at the investigator's discretion. However, they
             must test negative on the day of the surgery.

          8. Has a history of a clinically significant (in the investigator's opinion)
             gastrointestinal (GI) event within 6 months before Screening or has any history of
             peptic or gastric ulcers or GI bleeding.

          9. Has an active infection, mucositis, cold sores, viral lesions, local irritation, or in
             the investigator's opinion has significant periodontal disease of the oral cavity. In
             addition, recent (within 1 year) piercing of the tongue or anywhere in the oral
             cavity.

         10. Has a surgical or medical condition of the GI or renal system that, in the
             investigator's opinion, might significantly alter the absorption, distribution, or
             excretion of any drug substance.

         11. 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 Buprenorphine Sublingual Spray), to be an
             unsuitable candidate to receive the study drug.

         12. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been
             diagnosed with cancer within 5 years before Screening (excluding squamous or basal
             cell carcinoma of the skin).

         13. Is currently receiving anticoagulants (eg, heparin or warfarin). Low-dose aspirin for
             cardioprotection is allowed.

         14. Has used drugs known to be a strong inhibitor or inducer of CYP3A4 within 1 week
             before surgery.

         15. Has received a course of systemic corticosteroids (either oral or parenteral) within 1
             month before Screening (inhaled nasal steroids and topical corticosteroids are
             allowed).

         16. Has a history of chronic use (defined as daily use for >2 weeks) of NSAIDs, opiates,
             or glucocorticoids (except inhaled nasal steroids and topical corticosteroids) within
             1 month before study drug administration. Aspirin at a daily dose of ≤325 mg is
             allowed for cardiovascular prophylaxis if the participant has been on a stable dose
             regimen for ≥30 days before Screening and has not experienced any relevant medical
             problem.

         17. Has a significant renal or hepatic disease, as indicated by clinical laboratory
             assessment (results ≥3 × the upper limit of normal [ULN] for any liver function test,
             including aspartate aminotransferase, alanine aminotransferase, and lactate
             dehydrogenase, or creatinine ≥1.5 × ULN).

         18. Has any clinically significant laboratory or 12-lead electrocardiogram finding at
             Screening that in the investigator's opinion contraindicates study participation.

         19. Has screening systolic blood pressure ≥160 mmHg and diastolic blood pressure >100 mmHg
             (may be repeated one additional time after 5 minutes rest to verify). The investigator
             may, at his discretion, choose to exclude participants with hypertensive levels lower
             than these if he deems it in the best interest of the participant.

         20. Has a history of sleep apnea or other obstructive airway disease.

         21. Has a history of nausea and vomiting with buprenorphine products.

         22. Has significant difficulties swallowing capsules or is unable to tolerate oral
             medication.

         23. Previously participated in another clinical study of Buprenorphine Sublingual Spray or
             received any investigational drug or device or investigational therapy within 30 days
             before Screening.

        Post-surgical eligibility requirements:

        The participant will be assessed for the following postoperative eligibility criteria

          1. Participants must be awake, breathing spontaneously without significant respiratory
             depression.

          2. Participants must not be actively vomiting or complaining of severe nausea.

          3. Participants must be able to answer questions and follow commands.

          4. Participants must not have surgical complications that could compromise safety of the
             participant or confound the results of the study.