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

This is an interventional prevention trial for Postoperative Nausea and Vomiting Read More

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)