Clinical trial NCT02646566: Study of APD421 as PONV Treatment (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 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: 2016-01-05
Enrollment: 705
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 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 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.
* 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 (wound closure) 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 dopamine-antagonist agent likely to prevent or treat nausea or vomiting (given as prophylaxis or otherwise) in the period from 24 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 with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma.
* Patients with documented or suspected alcohol or substance abuse within the past 6 months.
* Patients with direct or indirect evidence of clinically significant hypokalaemia, such as a serum potassium level \< 3.0 mmol/L.
* 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.
* Patients who have a documented, clinically significant cardiac arrhythmia or congenital long QT syndrome.
* Patients who are pregnant or breast feeding.
* Patients being treated with levodopa.
* 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: Number of Participants With Complete Response (Success of Initial PONV Treatment)
timeFrame: 0-24 hours after administration of study medication
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 0-4 Hrs
timeFrame: 0-4 hours after administration of study medication
measure: Number of Participants With Complete Response 0-6 Hrs
timeFrame: 0-6 hours after administration of study medication
measure: Time to Treatment Failure
timeFrame: 0-24 hours after study drug administration
measure: Number of Patients With Incidence of Emesis
timeFrame: 30 mins to 24 hours after study drug administration
measure: Number of Patients Receiving Rescue Medication
timeFrame: 0-24 hours after study drug administration
measure: Number of Patients With an Incidence of Significant Nausea
timeFrame: 30 mins to 24 hours after study drug administration
measure: Number of Patients With an Incidence of Nausea
timeFrame: 30 mins to 24 hours after drug administration
measure: Maximum Severity of Nausea
timeFrame: 30 mins to 24 hours after study drug administration
measure: Evolution Score of Nausea (0-180 Mins)
timeFrame: 0-180 minutes after study drug administration
Other outcomes:
Locations:
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Strasbourg
country: France
facility: CHU de Hautepierre
city: Aue
country: Germany
facility: HELIOS Klinikum Aue
city: Heidelberg
country: Germany
facility: Universität Heidelberg
city: Marburg
country: Germany
facility: Philipps University
Study officials:
affiliation: Acacia Pharma Ltd
name: Gabriel Fox, MB BChir
role: STUDY_DIRECTOR
References: