Clinical trial NCT02449291: Study of APD421 as PONV Treatment (no Prior Prophylaxis)
Official title: Randomised, Double-blind, Placebo-controlled Study of APD421 (Amisulpride for IV Injection) as Treatment of Established Post-operative Nausea and Vomiting, in Patients Who Have Had no Prior Prophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Nausea and Vomiting
Lead sponsor: Acacia Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2015-05-20
Enrollment: 568
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Double-blind, randomised, parallel-group, placebo-controlled, adaptive, seamless, dose-selecting study to compare the efficacy of APD421 to placebo as treatment of established PONV, in patients who have not had prior PONV prophylaxis.


Eligibility criteria: Inclusion criteria:

* Male or female patients ≥ 18 years of age
* Provision of written informed consent
* 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
* Patients judged by the investigator to have a low to moderate 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
* 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 \<1% per year) between the date of screening and at least 48 hours after administration of study drug
* In order to be eligible for randomisation, subjects must also:

  (i) have experienced a first episode of PONV not more than 24 hours after the end of their operation and prior to discharge from hospital ("qualifying PONV episode"), for which they have not already received any anti-emetic treatment; and (ii) not have received any agent likely to prevent or treat nausea or vomiting (given as prophylaxis or otherwise) in the period from 12 hours prior to the start of their operation up to the time of the qualifying PONV episode.

Exclusion Criteria:

* Patients scheduled to undergo transplant surgery or any surgery where post-operative emesis may pose a significant danger to the patient
* Patients planned to receive only a local anaesthetic and/or regional neuraxial (intrathecal or epidural) block
* Patients who have received APD421 active ingredient for any indication within the last 2 weeks
* Patients who are allergic to APD421 active ingredient or any of the excipients of APD421
* Patients with a significant, ongoing history of vestibular disease or dizziness
* Patients being treated with regular anti-emetic therapy (dosed at least three times per week), which is still ongoing within one week prior to surgery
* Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma
* Patients being treated with levodopa
* Patients who are pregnant or breast feeding
* Patients with documented or suspected alcohol or substance abuse within the past 6 months
* Patients with a documented, clinically significant cardiac arrhythmia
* Patients diagnosed with Parkinson's disease
* Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks
* Patients with a history of epilepsy
* Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
* 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)
* Where local laws/regulations require: patients under legal protection

Primary outcomes:
measure: Complete Response (Success of Initial PONV Treatment)
timeFrame: 0-24 hours after treatment
Secondary outcomes:
measure: Number of Participants With Complete Response 0-2 Hrs
timeFrame: 0-2 hours after administration of study medication
measure: Number of Participants With Complete Response 2-24 Hrs
timeFrame: 2-24 hours after administration of study medication
measure: Time to Treatment Failure
timeFrame: 0-24 hours after study drug administration
measure: Number of Patients Experiencing Incidence of Emesis
timeFrame: 30 mins to 24 hours after study drug administration
measure: Number of Participants Using Rescue Medication
timeFrame: 0-24 hours after study drug administration
measure: Incidence of Significant Nausea
timeFrame: 30 mins to 24 hours after study drug administration
measure: Incidence of Nausea
timeFrame: 30 mins to 24 hours after study drug administration
measure: Maximum Severity of Nausea
timeFrame: 30 mins to 24 hours after study drug administration
measure: Evolution Score of Nausea (0-30 Mins)
timeFrame: 0-30 minutes after study drug administration
Other outcomes:
Locations:
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Strasbourg
country: France
facility: CHU de Hautepierre
city: Heidelberg
country: Germany
facility: Universität Heidelberg
Study officials:
affiliation: University of Miami
name: Keith Candiotti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Candiotti KA, Kranke P, Bergese SD, Melson TI, Motsch J, Siddiqui N, Chung F, Rodriguez Y, Minkowitz HS, Ayad SS, Diemunsch P, Fox G. Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis. Anesth Analg. 2019 Jun;128(6):1098-1105. doi: 10.1213/ANE.0000000000003733.