Phase II Dose-ranging Study of APD421 in PONV

Inclusion criteria

• Male or female patients ≥ 18 years of age
• Ability and willingness to give written informed consent
• Patients undergoing elective surgery under general anaesthesia requiring at least one overnight stay in hospital for either:

• Hysterectomy (any surgical technique)
• Cholecystectomy (any surgical technique)
• 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 of the following risk factors for PONV:

• Past history of PONV and/or motion sickness
• Habitual non-smoking status
• Female sex
• Expected to receive opioid analgesia post-operatively
• American Society of Anesthesiologists (ASA) risk score I-III
• 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
• Adequate haematological function

• Haemoglobin ≥ 9 g/dL
• White blood count ≥ 3.0 x 109/L
• Platelet count ≥ 100 x 109/L
• 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

• 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 who are expected to need a naso- or oral-gastric tube in situ after surgery is completed
• Patients receiving the active ingredient of APD421 for any indication within the last 2 weeks
• Patients who are allergic to the active ingredient or any of the excipients of APD421
• Patients with a pre-existing vestibular disorder or history of dizziness
• Patients with pre-existing nausea or vomiting in the 24 hours before surgery
• Patients treated with regular anti-emetic therapy including corticosteroids
• 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
• Patients being treated with levodopa
• Patients who are pregnant or breast feeding
• Patients with a history of alcohol abuse
• Patients with pre-existing, clinically significant cardiac arrhythmia
• Patients diagnosed with Parkinson's disease
• Patients who have received anti-cancer chemotherapy in the previous 4 weeks
• Patients with a history of epilepsy
• Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
• 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)