To assess the efficacy and safety of different doses of APD405 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.

Inclusion Criteria:

• Male or female patients ≥ 18 years of age

• Written informed consent

• 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

• Patients with at least 2 risk factors for PONV, defined as 2 of the following:

  1. Past history of PONV and/or motion sickness
  2. Non-smoking status
  3. Female gender
  4. Planned opiate use for post-operative analgesia

• American Society of Anesthesiologists (ASA) risk score I-III (see Appendix 3)

• Adequate hepatic and renal function

  • Alanine aminotransferase (ALT) <2.5 * upper limit normal (ULN)
  • Aspartate aminotransferase (AST) <2.5 * ULN
  • Bilirubin <1.5 * ULN
  • Creatinine <1.5 * ULN

• Adequate haematological function

  • Haemoglobin ≥9.5 g/dL
  • White blood count 4.0-11.0 * 10^9/L
  • Platelet count ≥150 - 400 * 10^9/L

• Ability and willingness to give written informed consent

Exclusion Criteria:

• Patients undergoing outpatient/day case surgery
• Patients undergoing surgery where the patient is expected to remain ventilated for a period after surgery
• Patients undergoing intra-thoracic, transplant or central nervous system surgery
• Patients receiving a local anaesthetic/regional neuraxial (intrathecal or epidural) block
• Patients receiving monoamine oxidase inhibitor (MAOI) therapy currently or in the preceding 3 weeks
• Patients with a pre-existing vestibular disorder or history of dizziness
• Patients that are expected to need a naso- or oral-gastric tube in situ after surgery is completed
• Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
• Patients treated with regular anti-emetic therapy including corticosteroids
• Patients receiving CYP3A4 inducers or inhibitors within 7 days prior to study including but not limited to erythromycin, itraconazole, nefazodone, diltiazem, verapamil, rifampicin
• Patients with pre-existing nausea or vomiting 24 hours before surgery
• Patients who are breast feeding or pregnant
• Patients with a history of alcohol abuse
• Patients diagnosed with Parkinson's disease
• Patients who have received anti-cancer chemotherapy in the previous 4 weeks
• Patients with pre-existing clinically significant cardiac arrhythmia
• Patients with a history of epilepsy
• 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)