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
DRUGPlacebo
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 |
|---|---|---|
| Complete Response (no Emesis, Significant Nausea or Rescue Medication) | 24 hours after end of surgery | The primary efficacy analysis was a comparison of the incidence of Complete Response (absence of PONV1) in the 0-24-hour period after surgery, between the active treatment group and the placebo group using Pearson square test with Yates's continuity correction at a two-sided significance level of 5%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Response (no Emesis, Nausea or Rescue Medication) | 24 hrs after end of surgery | — |
| Incidence of Emesis (Vomiting/Retching) | 24 hours after end of surgeryry | An assessment of a participant experiencing an episode of emesis (vomiting/ retching) or received anti-emetic rescue medication during the 24hours after the completion of the surgery |
| Complete Response (no Emesis or Rescue Medication) | 24 hrs after end of surgery | — |
| Incidence of Significant Nausea | 24 hours after end of surgery | Count of participants with nausea score ≥ 4 on 0-10 verbal response scale |
| Use of Rescue Medication | 24 hours after end of surgery | — |
| Incidence of Nausea | 24 hours after end of surgery | Count of patients experiencing an episode of nausea scored ≥ 1 of 0-10 verbal response scale during the 24 hours period after the completion of surgery |
Countries
France, Germany
Participant flow
Pre-assignment details
Of the 368 patients enrolled in the study, 21 patients were not randomised and not dosed. Of these, 3 withdrew their consent, 5 did not comply with the protocol procedures and 13 were not dosed for other unspecified reasons.
Participants by arm
| Arm | Count |
|---|---|
| APD421 APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia. | 169 |
| Placebo Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia. | 178 |
| Total | 347 |
Baseline characteristics
| Characteristic | APD421 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.7 Years STANDARD_DEVIATION 16.2 | 51.6 Years STANDARD_DEVIATION 14.9 | 51.6 Years STANDARD_DEVIATION 15.5 |
| Sex: Female, Male Female | 147 Participants | 154 Participants | 301 Participants |
| Sex: Female, Male Male | 22 Participants | 24 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 169 | 0 / 178 |
| other Total, other adverse events | 91 / 169 | 178 / 178 |
| serious Total, serious adverse events | 3 / 169 | 4 / 178 |
Outcome results
Primary
Complete Response (no Emesis, Significant Nausea or Rescue Medication)
The primary efficacy analysis was a comparison of the incidence of Complete Response (absence of PONV1) in the 0-24-hour period after surgery, between the active treatment group and the placebo group using Pearson square test with Yates's continuity correction at a two-sided significance level of 5%.
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Complete Response (no Emesis, Significant Nausea or Rescue Medication) | 95 Participants |
| Placebo | Complete Response (no Emesis, Significant Nausea or Rescue Medication) | 83 Participants |
Comparison: The primary efficacy analysis was a complete response which is defined as protection from PONV1, which was absence of any episode of emesis, significant nausea or use of rescue medication with the first 24 hours post-operatively.p-value: 0.093Chi-squared, Corrected
Secondary
Complete Response (no Emesis or Rescue Medication)
Time frame: 24 hrs after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Complete Response (no Emesis or Rescue Medication) | 100 Participants |
| Placebo | Complete Response (no Emesis or Rescue Medication) | 89 Participants |
p-value: 0.059Chi-squared, Corrected
Secondary
Incidence of Emesis (Vomiting/Retching)
An assessment of a participant experiencing an episode of emesis (vomiting/ retching) or received anti-emetic rescue medication during the 24hours after the completion of the surgery
Time frame: 24 hours after end of surgeryry
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Incidence of Emesis (Vomiting/Retching) | 34 Participants |
| Placebo | Incidence of Emesis (Vomiting/Retching) | 46 Participants |
p-value: 0.26Chi-squared, Corrected
Secondary
Incidence of Nausea
Count of patients experiencing an episode of nausea scored ≥ 1 of 0-10 verbal response scale during the 24 hours period after the completion of surgery
Time frame: 24 hours after end of surgery
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Incidence of Nausea | 75 Participants |
| Placebo | Incidence of Nausea | 98 Participants |
p-value: 0.06Chi-squared, Corrected
Secondary
Incidence of Significant Nausea
Count of participants with nausea score ≥ 4 on 0-10 verbal response scale
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Incidence of Significant Nausea | 63 Participants |
| Placebo | Incidence of Significant Nausea | 84 Participants |
p-value: 0.079Chi-squared, Corrected
Secondary
Total Response (no Emesis, Nausea or Rescue Medication)
Time frame: 24 hrs after end of surgery
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Total Response (no Emesis, Nausea or Rescue Medication) | 87 Participants |
| Placebo | Total Response (no Emesis, Nausea or Rescue Medication) | 73 Participants |
p-value: 0.053Chi-squared, Corrected
Secondary
Use of Rescue Medication
Time frame: 24 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APD421 | Use of Rescue Medication | 62 Participants |
| Placebo | Use of Rescue Medication | 82 Participants |
p-value: 0.096Chi-squared, Corrected