A Study of TAK-951 to Stop Adults Getting Nausea and Vomiting After Planned Surgery
Condition: Postoperative Nausea and Vomiting (PONV)
MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting
Intervention: TAK-951; Ondansetron; Ondansetron Placebo; TAK-951 Placebo
Intervention description: TAK-951 SC injection; Ondansetron IV injection; Ondansetron placebo-matching IV injection; TAK-951 placebo-matching SC injection
Intervention MeSH terms: Ondansetron
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      Some adults are at a higher risk of feeling sick (nausea) or being sick (vomiting) after they
      have surgery. In this study, these adults will have planned surgery. The main aim of this
      study is to learn if TAK-951 stops these adults from getting nausea or vomiting after
      surgery. This will be compared with another medicine called ondansetron. Another aim is to
      check for side effects from the study medicines.

      Before surgery, the study doctor will check who can take part in this study. Those who can
      take part will be picked for either Treatment Group A or Treatment Group B by chance.

        -  Treatment Group A: Just before surgery, participants will receive a placebo slowly
           through a vein (infusion). Just before the end of the surgery, they will receive TAK-951
           as an injection under the skin.

        -  Treatment Group B: Just before surgery, participants will receive ondansetron slowly
           through a vein (infusion). Just before the end of the surgery, they will receive a
           placebo as an injection under the skin. In this study, a placebo will look like TAK-951
           but will not have any medicine in it.

      Participants will not know which study medicines they received, or in which order, nor will
      their study doctors or surgeons. This is to help make sure the results are more reliable.

      Participants will stay in the hospital for 24 hours after their surgery so that the study
      doctors can check for nausea and vomiting. The study doctors will also check for side effects
      from the study medicines.

      Participants will visit the hospital for a check-up 14 days later.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants undergoing elective surgery under general anesthesia, expected to last
             for at least 1 hour from induction of anesthesia to wound closure.

          2. Participants are expected to require or have agreed to stay, at least 1 overnight in
             the hospital.

          3. Participants American Society of Anesthesiologists (ASA) physical status is ASA I-III.

          4. Participants with 3 or more Apfel risk factors defined as:

               1. Female sex.

               2. Nonsmoking status (never smoked or stopped smoking ≥12 months ago).

               3. History of PONV or motion sickness.

               4. Planned use of postoperative opioid analgesics.

        Exclusion Criteria:

          1. Participants who are expected to remain intubated post-anesthesia.

          2. Participants who experience nausea or vomiting within 24 hours before surgery or are
             diagnosed with gastroparesis, cyclic vomiting syndrome, or other condition associated
             with acute or chronic nausea and vomiting.

          3. Participants who have received, or are expected to receive, any excluded drug
             preoperatively within 24 hours before induction, during surgery, or within 24 hours
             after surgery.

          4. Participants scheduled to receive neuraxial anesthesia (e.g., epidural, spinal, or
             caudal anesthesia), regional blocks, or total IV anesthesia, and/or planned to receive
             different drugs for premedication, induction, maintenance, or reversal of anesthesia
             than those specified in the protocol.

          5. Participants who have an allergy or contraindication to the recommended and available
             rescue therapy for the treatment of PONV.

          6. Circumstance that, in the investigator's opinion, make participation in this clinical
             study inappropriate.

          7. Participants found at the screening to have a QT interval with Fridericia correction
             method (QTcF) ≥450 msec or other factors that increase the risk of QT prolongation or
             arrhythmic events. Assessments showing bundle branch block and a prolonged QTcF should
             be discussed with the study monitor and the sponsor for potential inclusion.

          8. Participants who have a direct family history of premature sudden death or
             channelopathy, personal history of Brugada syndrome (right bundle branch block pattern
             with ST elevation in leads V1-V3), long QT, short QT, arrhythmogenic right ventricular
             dysplasia, hypertrophic cardiomyopathy or catecholaminergic polymorphic ventricular
             tachycardia (VT).

          9. Participants who have had 3 incidents of vasovagal syncope within the last 5 years.

         10. Participants with an average heart rate (HR) <55 or >100 bpm or systolic blood
             pressure (SBP) <90 mm Hg or Diastolic blood pressure (DBP) <60 mm Hg during screening
             or prior to randomization on the day of surgery.

         11. Participants with a clinically significant ECG abnormality indicative of acute cardiac
             instability as determined by the investigator at screening, including more than
             first-degree atrioventricular block, nonsustained or sustained VT, or ECG changes
             consistent with acute myocardial ischemia or infarction.

         12. Participants with a history of acute myocardial ischemia within the last 12 months.

         13. Participants receiving beta-blockers chronically or between screening and surgery that
             cannot be safely withheld on the day of surgery in the investigator's judgment.
             Participants receiving certain other cardiovascular medications, such as vasodilators
             for hypertension, chronically or between screening and surgery that in the
             investigator's judgment cannot be adequately managed in the perioperative setting
             considering the potential vasodilatory effects of TAK-951 and anesthesia standard of
             care. The investigators must consult with the medical monitor regarding the
             eligibility of participants who are receiving beta-blockers, vasodilators, and other
             classes of medications that act on HR or BP.

         14. Participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
             >2 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN.