Dose-ranging Study of APD405 in Post-operative Nausea and Vomiting (PONV)

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)