Clinical trial NCT00895830: Dose-ranging Study of APD405 in Post-operative Nausea and Vomiting (PONV)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Nausea and Vomiting
Lead sponsor: Acacia Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2009-05-08
Enrollment: 257
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Experienced Post-operative Nausea or Vomiting
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Medical Center at Mt Zion
state: California
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: Memorial Hermann-Memorial City Hospital
state: Texas
city: Besançon
country: France
facility: University Hospital
city: Bron
country: France
facility: Hôpital mère enfant
city: Lille
country: France
facility: Hôpital Huriez
city: Nancy
country: France
facility: University Hospital
city: Paris
country: France
facility: Hôpital FOCH
city: Reims
country: France
facility: University Hospital
city: Strasbourg
country: France
facility: Hautepierre Hospital
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin
city: Heidelberg
country: Germany
facility: Universität Heidelberg
city: Leipzig
country: Germany
facility: University of Leipzig
city: Ludwigshafen
country: Germany
facility: Klinikum Ludwigshafen
city: Marburg
country: Germany
facility: Philipps University
city: Würzburg
country: Germany
facility: University Hospitals of Würzburg
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: University Hospital, Geneva
name: Martin Tramèr, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kranke P, Rohm KD, Diemunsch P, Gan TJ, Apfel CC, Eberhart L, Minkowitz HS, Wallenborn J, Chassard D, Lebuffe G, Fox GM, Tramer MR. Intravenous buspirone for the prevention of postoperative nausea and vomiting. Eur J Clin Pharmacol. 2012 Nov;68(11):1465-72. doi: 10.1007/s00228-012-1284-8. Epub 2012 May 1.