Post-operative nausea and vomiting MedDRA version: 19.0 Level: PT Classification code 10066962 Term: Procedural nausea System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Sponsors
Acacia Pharma Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients = 18 years of age. 2. Provision of written informed consent. 3. Patients scheduled to undergo elective surgery (open or laparoscopic technique) under general anaesthesia (other than total intravenous anaesthesia with propofol) expected to last at least one hour from induction of anaesthesia to extubation. 4. Patients judged by the investigator to have a moderate or high risk of experiencing PONV. In forming this judgment, investigators should pay particular attention to risk factors such as a past history of PONV and/or motion sickness; habitual non-smoking status; female sex; and likely use of opioid analgesia post-operatively. 5. For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (as defined in ICH M3 guidance, e.g., abstinence from sexual intercourse, surgical sterilisation (of subject or partner), combined oral contraceptive pill, 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, or any other method or combination of methods with a failure rate generally considered to be =65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: 1. Patients scheduled to undergo transplant surgery or any surgery where post-operative emesis may pose a significant danger to the patient. 2. Patients planned to receive only a local anaesthetic and/or regional neuraxial (intrathecal or epidural) block. 3. Patients who have received amisulpride for any indication within the last 2 weeks. 4. Patients who are allergic to amisulpride or any of the excipients of APD421. 5. Patients with a significant, ongoing history of vestibular disease or dizziness. 6. Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma. 7. Patients with documented or suspected alcohol or substance abuse within the past 6 months. 8. Patients with direct or indirect evidence of clinically significant hypokalaemia, such as a serum potassium level < 3.0 mmol/L. 9. Patients who have received in the post-operative period, and prior to receiving study drug, any medication with a substantial risk of inducing 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, etc. 10. Patients who have a documented, clinically significant cardiac arrhythmia or congenital long QT syndrome. 11. Patients who are pregnant or breast feeding. 12. Patients being treated with levodopa. 13. Patients diagnosed with Parkinson’s disease. 14. Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks. 15. Patients with a history of epilepsy. 16. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study. 17. Patients who have previously participated in this study or who have participated in another interventional clinical study involving pharmacological therapy within the previous 28 days (or longer exclusion period, if required by national or local regulations). 18. Patients under legal protection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of 5 mg and 10 mg APD421 to placebo as treatment of established PONV, in patients who have had prior PONV prophylaxis;Secondary Objective: - To assess the safety and tolerability of APD421 given as treatment for PONV ;Primary end point(s): Success in primary PONV treatment, defined as no emetic episodes from 30 minutes to 24 hours after administration of study medication and no administration of further anti-emetic medication at any time in the 24-hour period after administration of study medication.;Timepoint(s) of evaluation of this end point: Primary endpoints will be assessed during the period beginning with the first episode of PONV, ending 24 hours after administration of study medication. Nausea assessment then completed at 5, 15, 30 and 120 minutes after administration. Vomiting, retching and requirement for rescue medication continually assessed throughout the 24 hour period following administration of study drug/placebo. If patient already discharged prior to 24 hrs: emesis, nausea and rescue medication assessments to be done via patient diary and telephone follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: - The occurrence and severity of nausea and of significant nausea, including measures of the time course of nausea, such as area under the curve for nausea scores for time periods up to 24 hours. -The occurrence of vomiting (to include retching) after administration of study medication - Use of anti-emetic rescue medication (see Section 5.3 regarding use of rescue medication) - Time to failure of primary treatment - Sub-analyses of success and failure according to various parameters, including by time of onset of PONV relative to end of surgery and by sex - Time to discharge from PACU/recovery unit and hospital/clinic Safety: - The nature and frequency of adverse events and laboratory abnormalities;Timepoint(s) of evaluation of this end point: Nausea assessment will be assessed during the period beginning with the first episode of PONV. Nausea assessment then completed at 5, 15, 30 and 120 minutes after administration. Vomiting, retching and requirement for rescue medication continually assessed throughout the 24 hour period following administration of study drug/placebo. If patient already discharged prior to 24 hrs: emesis, nausea and rescue medication assessments to be done via patient diary and telephone follow-up. Blood samples taken post operatively, 5, 30 and 120 minutes following administration and then 6, 24 hours and at discharge for pK. Samples for blood chemistry and haematology taken post operatively, and then at 1 hour prior to discharge or 24 hours post administration (whichever is earlier). | — |
Countries
Canada, France, Germany, United States
Contacts
Public ContactClinical Trials Information
Acacia Pharma Ltd
Outcome results
None listed