Clinical trial NCT01510704: Phase II Dose-ranging Study of APD421 in PONV
Official title: Randomised, Double-blind, Placebo-controlled, Dose-ranging Phase II Study of APD421 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: 2012-01-16
Enrollment: 215
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 APD421 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

1. Male or female patients ≥ 18 years of age
2. Ability and willingness to give written informed consent
3. 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
4. Patients with at least 2 of the following risk factors for PONV:

   1. Past history of PONV and/or motion sickness
   2. Habitual non-smoking status
   3. Female sex
   4. Expected to receive opioid analgesia post-operatively
5. American Society of Anesthesiologists (ASA) risk score I-III
6. 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
7. Adequate haematological function

   * Haemoglobin ≥ 9 g/dL
   * White blood count ≥ 3.0 x 109/L
   * Platelet count ≥ 100 x 109/L
8. 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

1. Patients undergoing outpatient/day case surgery
2. Patients undergoing surgery where the patient is expected to remain ventilated for a period after surgery
3. Patients undergoing intra-thoracic, transplant or central nervous system surgery
4. Patients receiving a local anaesthetic/regional neuraxial (intrathecal or epidural) block
5. Patients who are expected to need a naso- or oral-gastric tube in situ after surgery is completed
6. Patients receiving the active ingredient of APD421 for any indication within the last 2 weeks
7. Patients who are allergic to the active ingredient or any of the excipients of APD421
8. Patients with a pre-existing vestibular disorder or history of dizziness
9. Patients with pre-existing nausea or vomiting in the 24 hours before surgery
10. Patients treated with regular anti-emetic therapy including corticosteroids
11. 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
12. Patients being treated with levodopa
13. Patients who are pregnant or breast feeding
14. Patients with a history of alcohol abuse
15. Patients with pre-existing, clinically significant cardiac arrhythmia
16. Patients diagnosed with Parkinson's disease
17. Patients who have received anti-cancer chemotherapy in the previous 4 weeks
18. Patients with a history of epilepsy
19. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
20. 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: Post-operative Nausea or Vomiting
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
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: Strasbourg
country: France
facility: Hautepierre Hospital
city: Aue
country: Germany
facility: HELIOS Klinikum Aue
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin
city: Heidelberg
country: Germany
facility: Universität Heidelberg
city: Ludwigshafen
country: Germany
facility: Klinikum Ludwigshafen
city: Marburg
country: Germany
facility: Philipps University
city: Würzburg
country: Germany
facility: University Hospitals of Würzburg
Study officials:
affiliation: University Hospitals of Würzburg
name: Peter Kranke, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kranke P, Eberhart L, Motsch J, Chassard D, Wallenborn J, Diemunsch P, Liu N, Keh D, Bouaziz H, Bergis M, Fox G, Gan TJ. I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial. Br J Anaesth. 2013 Dec;111(6):938-45. doi: 10.1093/bja/aet251. Epub 2013 Jul 19.