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

Study Overview
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Brief Summary
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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.

Official Title
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Randomised, Double-blind, Placebo-controlled, Phase II Study to Assess the Safety and Efficacy of Different Doses of Intravenous APD405 for the Prevention of Post-operative Nausea and Vomiting

Conditions
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Postoperative Nausea and Vomiting

Intervention / Treatment
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* Drug: APD405
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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 risk factors for PONV, defined as 2 of the following: Past history of PONV and/or motion sickness Non-smoking status Female gender 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo<br>* IV<br>|
| Experimental: 2<br>0.3mg dose level | Drug: APD405<br>* IV<br>|
| Experimental: 3<br>1mg dose level | Drug: APD405<br>* IV<br>|
| Experimental: 4<br>2mg dose level | Drug: APD405<br>* IV<br>|
| Experimental: 5<br>3mg dose level | Drug: APD405<br>* IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Experienced Post-operative Nausea or Vomiting |  | 24 hours |