Phase II Dose-ranging Study of APD421 in PONV
Condition: Postoperative Nausea and Vomiting
MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting
Intervention: APD421; Placebo
Intervention description: IV; IV
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To assess the efficacy and safety of different doses of APD421 in the prevention of
      post-operative nausea and vomiting (PONV) in adult patients at moderate to high-risk of PONV.
      Patients must be undergoing elective surgery under general anaesthesia (hysterectomy (any
      surgical technique), cholecystectomy (any surgical technique) or "other" elective surgery
      scheduled to last at least one hour from induction of anaesthesia), requiring at least one
      overnight stay in hospital, and have at least 2 of the following risk factors for PONV: Past
      history of PONV and/or motion sickness; Non-smoking status; Female gender; Planned opiate use
      for post-operative analgesia.
    

Eligibility criteria:

        Inclusion criteria

          1. Male or female patients ≥ 18 years of age

          2. Ability and willingness to give written informed consent

          3. Patients undergoing elective surgery under general anaesthesia requiring at least one
             overnight stay in hospital for either:

               1. Hysterectomy (any surgical technique)

               2. Cholecystectomy (any surgical technique)

               3. Other elective surgery requiring overnight admission to hospital and scheduled to
                  last at least 1 hour from induction of anaesthesia

          4. Patients with at least 2 of the following risk factors for PONV:

               1. Past history of PONV and/or motion sickness

               2. Habitual non-smoking status

               3. Female sex

               4. Expected to receive opioid analgesia post-operatively

          5. American Society of Anesthesiologists (ASA) risk score I-III

          6. Adequate cardiac, hepatic and renal function

               -  QTc interval < 500 ms

               -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 5 x
                  upper limit normal (ULN)

               -  Bilirubin < 3 x ULN

               -  Creatinine < 2 x ULN

          7. Adequate haematological function

               -  Haemoglobin ≥ 9 g/dL

               -  White blood count ≥ 3.0 x 109/L

               -  Platelet count ≥ 100 x 109/L

          8. For females of child-bearing potential: ability and willingness to use a highly
             effective form of contraception (e.g., abstinence from sexual intercourse, surgical
             sterilisation (of subject or partner) or a double-barrier method of contraception such
             as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in
             conjunction with partner's use of a condom) between the date of screening and at least
             48 hours after administration of study drug.

        Exclusion Criteria

          1. Patients undergoing outpatient/day case surgery

          2. Patients undergoing surgery where the patient is expected to remain ventilated for a
             period after surgery

          3. Patients undergoing intra-thoracic, transplant or central nervous system surgery

          4. Patients receiving a local anaesthetic/regional neuraxial (intrathecal or epidural)
             block

          5. Patients who are expected to need a naso- or oral-gastric tube in situ after surgery
             is completed

          6. Patients receiving the active ingredient of APD421 for any indication within the last
             2 weeks

          7. Patients who are allergic to the active ingredient or any of the excipients of APD421

          8. Patients with a pre-existing vestibular disorder or history of dizziness

          9. Patients with pre-existing nausea or vomiting in the 24 hours before surgery

         10. Patients treated with regular anti-emetic therapy including corticosteroids

         11. Patients being treated with medications which could induce torsades de pointes,
             including Class Ia antiarrhythmic agents such as quinidine, disopyramide,
             procainamide; Class III antiarrhythmic agents such as amiodarone and sotalol; and
             other medications such as bepridil, cisapride, thioridazine, methadone, IV
             erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin

         12. Patients being treated with levodopa

         13. Patients who are pregnant or breast feeding

         14. Patients with a history of alcohol abuse

         15. Patients with pre-existing, clinically significant cardiac arrhythmia

         16. Patients diagnosed with Parkinson's disease

         17. Patients who have received anti-cancer chemotherapy in the previous 4 weeks

         18. Patients with a history of epilepsy

         19. Any other concurrent disease or illness that, in the opinion of the investigator makes
             the patient unsuitable for the study

         20. Patients who have participated in a previous study within the last 28 days (French
             sites only: Patients who have participated in a previous study within the last 6
             months, if required by national or local regulations)