US Phase III Study of APD421 in PONV

Study Overview
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Brief Summary
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A comparison of the efficacy of APD421 and placebo in the prevention of PONV in patients at moderate-to-high risk of PONV.

Official Title
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Randomized, Double-blind, Placebo-controlled Phase III Study of APD421 (Amisulpride for IV Injection) as Prophylaxis Against Post-operative Nausea and Vomiting

Conditions
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PONV

Intervention / Treatment
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* Drug: APD421- Amisulpride for IV injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 18 years of age Patients undergoing elective surgery (open or laparoscopic technique) under general anaesthesia, expected to last at least one hour from induction of anaesthesia to wound closure and expected to require at least one overnight stay in hospital Exclusion Criteria: Patients scheduled for outpatient/day case surgery Patients scheduled to undergo intra-thoracic, transplant or central nervous system surgery Patients scheduled to receive only a local anaesthetic/regional neuraxial (intrathecal or epidural) block Patients who are expected to remain ventilated for a period after surgery Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APD421<br>APD421 (amisulpride), at 5mg given by single intravenous (IV) administration by slow push over one minute at induction of anaesthesia. | Drug: APD421- Amisulpride for IV injection<br>* APD421 ( Amisulpride) at 5mg given by single intravenous (IV) administration, by slow push over one minute, at induction of anaesthesia<br>* Other names: Amisulpride for IV injection;|
| Placebo Comparator: Placebo<br>Matching placebo given by single IV administration by slow push over one minute at induction of anaesthesia | Drug: Placebo<br>* Matching Placebo given by single intravenous (IV) administration, by slow push over one minute, at induction of anaesthesia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Response | The primary efficacy analysis was a comparison of the incidence of Complete Response, defined as no emesis (vomiting or retching) and no use of rescue medication in the 24 hours after the end of surgery, between the active group and the placebo group using Pearson χ2 test with Yates's continuity correction, and with a two-sided significance level of 5%. | 24 hours after the end of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With no Nausea. | Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. No nausea means no score ≥ 1. | 24 hours after end of surgery | 
| Number of Participants With no Emesis | Emesis is defined as vomiting (production of even the smallest amount of stomach contents) or retching (muscular movements of vomiting but without expulsion of stomach contents, usually because of an empty stomach) | 24 hours after end of surgery | 
| Number of Participants With no Use of Rescue Medication | Any agent given in the post-operative period with the intention of providing anti-emetic rescue was counted as rescue anti-emetic medication for the purposes of efficacy determination, even if it did not achieve control of emesis or was given incorrectly (e.g., wrong dosage or route). Any agent given in the post-operative period which would be expected, by virtue of its pharmacology, dosage and route, to exert a clinically meaningful anti-emetic effect was considered as rescue anti-emetic medication, even if administered inadvertently or without the intention of providing rescue. | 24 hours after end of surgery | 
| The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication | No occurrence of vomiting/retching, no nausea score ≥ 4 on verbal response scale (where 0=no nausea at all and 10=the worst nausea imaginable) and no use of rescue medication. | 24 hours after the end of surgery | 
| The Number of Participants With no Significant Nausea | Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. No significant nausea means no score ≥ 4. | 24 hours after the end of surgery | 
| Number of Participants With Total Response | Total response is defined as no occurrence of vomiting/retching, no nausea score ≥ 1 and no use of rescue medication. | 24 hours after the end of surgery |