PONV
Conditions
Brief summary
A comparison of the efficacy of APD421 and placebo in the prevention of PONV in patients at moderate-to-high risk of PONV.
Interventions
DRUGAPD421- Amisulpride for IV injection
APD421 ( Amisulpride) at 5mg given by single intravenous (IV) administration, by slow push over one minute, at induction of anaesthesia
DRUGPlacebo
Matching Placebo given by single intravenous (IV) administration, by slow push over one minute, at induction of anaesthesia
Sponsors
Acacia Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response | 24 hours after the end of surgery | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With no Emesis | 24 hours after end of surgery | 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) |
| Number of Participants With no Use of Rescue Medication | 24 hours after end of surgery | 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. |
| Number of Participants With no Nausea. | 24 hours after end of surgery | 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. |
| The Number of Participants With no Significant Nausea | 24 hours after the end of surgery | 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. |
| Number of Participants With Total Response | 24 hours after the end of surgery | Total response is defined as no occurrence of vomiting/retching, no nausea score ≥ 1 and no use of rescue medication. |
| The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication | 24 hours after the end of surgery | 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. |
Countries
United States
Participant flow
Pre-assignment details
Of the 364 patients enrolled in the study (i.e. signed informed consent form), 22 patients were not randomised and not dosed. Of these, 4 withdrew their consent, 3 did not comply with the protocol procedures and 15 were not dosed for other unspecified reasons.
Participants by arm
| Arm | Count |
|---|---|
| 5mg Dose APD421 A 5mg dose of APD421 given by slow push, single intravenous (IV) administration over a time frame of one minute at induction of anaesthesia | 176 |
| Placebo Single dose placebo given through intravenous (IV) administration | 166 |
| Total | 342 |
Baseline characteristics
| Characteristic | 5mg Dose APD421 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.5 Years STANDARD_DEVIATION 14.2 | 53.0 Years STANDARD_DEVIATION 13.7 | 53.8 Years STANDARD_DEVIATION 13.9 |
| Region of Enrollment United States | 176 participants | 166 participants | 342 participants |
| Sex: Female, Male Female | 114 Participants | 110 Participants | 224 Participants |
| Sex: Female, Male Male | 62 Participants | 56 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 176 | 0 / 166 |
| other Total, other adverse events | 169 / 176 | 160 / 166 |
| serious Total, serious adverse events | 8 / 176 | 9 / 166 |
Outcome results
Primary
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%.
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | Number of Participants With Complete Response | 78 Participants |
| Placebo | Number of Participants With Complete Response | 54 Participants |
p-value: 0.033Chi-squared, Corrected
Secondary
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)
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | Number of Participants With no Emesis | 141 Participants |
| Placebo | Number of Participants With no Emesis | 129 Participants |
p-value: 0.68Chi-squared, Corrected
Secondary
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.
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | Number of Participants With no Nausea. | 82 Participants |
| Placebo | Number of Participants With no Nausea. | 64 Participants |
p-value: 0.16Chi-squared, Corrected
Secondary
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.
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | Number of Participants With no Use of Rescue Medication | 80 Participants |
| Placebo | Number of Participants With no Use of Rescue Medication | 55 Participants |
p-value: 0.026Chi-squared, Corrected
Secondary
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.
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | Number of Participants With Total Response | 67 Participants |
| Placebo | Number of Participants With Total Response | 50 Participants |
p-value: 0.15Chi-squared, Corrected
Secondary
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.
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication | 73 Participants |
| Placebo | The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication | 53 Participants |
p-value: 0.086Chi-squared, Corrected
Secondary
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.
Time frame: 24 hours after the end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 at 5mg | The Number of Participants With no Significant Nausea | 107 Participants |
| Placebo | The Number of Participants With no Significant Nausea | 84 Participants |
p-value: 0.074Chi-squared, Corrected